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Microenvironmental pH is a key factor for exosome traffic in tumor cells - PubMed
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class="collections-new" name="collections" value="new" data-ga-category="save_share" data-ga-action="collections" data-ga-label="collections_radio_new"> <label for="collections-action-panel-new">Create a new collection</label> </li> <li> <input type="radio" id="collections-action-panel-existing" class="collections-existing" name="collections" value="existing" checked="true" data-ga-category="save_share" data-ga-action="collections" data-ga-label="collections_radio_existing"> <label for="collections-action-panel-existing">Add to an existing collection</label> </li> </ul> </div> <div class="controls-wrapper"> <div class="action-panel-control-wrap new-collections-controls"> <label for="collections-action-panel-add-to-new" class="action-panel-label required-field-asterisk"> Name your collection: </label> <input type="text" name="add-to-new-collection" id="collections-action-panel-add-to-new" class="collections-action-add-to-new" pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/" maxlength="100" data-ga-category="save_share" data-ga-action="create_collection" data-ga-label="non_favorties_collection"> <div class="collections-new-name-too-long usa-input-error-message selection-validation-message"> Name must be less than 100 characters </div> </div> <div class="action-panel-control-wrap existing-collections-controls"> <label for="collections-action-panel-add-to-existing" class="action-panel-label"> Choose a collection: </label> <select id="collections-action-panel-add-to-existing" class="action-panel-selector collections-action-add-to-existing" data-ga-category="save_share" data-ga-action="select_collection" data-ga-label="($('#collections-action-add-to-existing').val() === 'Favorites') ? 'Favorites' : 'non_favorites_collection'"> </select> <div class="collections-retry-load-on-error usa-input-error-message selection-validation-message"> Unable to load your collection due to an error<br> <a href="#">Please try again</a> </div> </div> </div> <div class="action-panel-actions"> <button class="action-panel-submit" type="submit" data-loading-label="Adding..." data-pinger-ignore data-ga-category="save_share" data-ga-action="collections" data-ga-label="add"> Add </button> <button class="action-panel-cancel" aria-label="Close 'Add to Collections' panel" ref="linksrc=close_collections_panel" aria-controls="collections-action-panel" aria-expanded="false" data-ga-category="save_share" data-ga-action="collections" data-ga-label="cancel"> Cancel </button> </div> </form> </div> </div> <div id="bibliography-action-panel" class="bibliography-action-panel action-panel in-progress-dots-panel" aria-hidden="true" data-bibliography-open-panel-enabled="false" data-bibliography-open-panel-url-hash="#open-bibliography-panel"> <div class="inner-wrap"> <h3 class="action-panel-heading"> Add to My Bibliography </h3> <form id="bibliography-action-panel-form" class="bibliography-action-panel-form action-panel-content action-form action-panel-smaller-selectors" data-add-to-bibliography-max-amount="100" data-add-to-bibliography-batch-size="10" data-bibliography-delegates-url="/list-bibliography-delegates/" data-add-to-bibliography-url="/add-to-bibliography/" data-get-article-ids-by-search-url="/get-article-ids-by-search/" data-mybib-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/mybibliography/"> <input type="hidden" name="csrfmiddlewaretoken" value="Sni8ogOUNwSfyfPovgvqqKpNKH96r3M98fT47VPtFSprCFdFnkog6SHQSm21VDgZ"> <div class="action-panel-control-wrap bibliographies-controls"> <div class="choice-group"> <ul class="bibliographies-action-add radio-group-items"> <li> <input name="bibliography" id="my-bibliography" class="my-bibliography" type="radio" checked/> <label for="my-bibliography">My Bibliography</label> </li> </ul> </div> </div> <div class="bibliographies-retry-load-on-error usa-input-error-message selection-validation-message"> Unable to load your delegates due to an error<br> <a href="#">Please try again</a> </div> <div class="action-panel-actions"> <button class="action-panel-submit" type="submit" data-loading-label="Adding..." data-pinger-ignore> Add </button> <button class="action-panel-cancel" aria-label="Close 'Add to bibliography' panel" ref="linksrc=close_bibliography_panel" aria-controls="bibliography-action-panel" aria-expanded="false" data-ga-category="save_share" data-ga-action="mybib" data-ga-label="cancel"> Cancel </button> </div> </form> </div> </div> <div id="saved-search-action-panel" class="saved-search-action-panel action-panel " aria-hidden="true" data-saved-search-open-panel-enabled="false" data-saved-search-open-panel-url-hash="#open-saved-search-panel"> <div class="inner-wrap"> <h2 class="action-panel-heading"> Your saved search </h2> <form id="saved-search-action-panel-form" class="saved-search-action-panel-form action-panel-content action-form" data-create-saved-search-url="/create-saved-search/" data-try-search-terms-url="/try-search-term/" data-saved-search-root-url="https://www.ncbi.nlm.nih.gov/myncbi/searches/"> <input type="hidden" name="csrfmiddlewaretoken" value="Sni8ogOUNwSfyfPovgvqqKpNKH96r3M98fT47VPtFSprCFdFnkog6SHQSm21VDgZ"> <div class="action-panel-control-wrap"> <label for="saved-search-name" class="action-panel-label saved-search-name-label required-field-asterisk"> Name of saved search: </label> <input maxlength="200" type="text" name="saved-search-name" id="saved-search-name" class="saved-search-name" value="" required pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/"> </div> <div class="action-panel-control-wrap"> <label for="saved-search-term" class="action-panel-label required-field-asterisk"> Search terms: </label> <textarea name="saved-search-term" id="saved-search-term" class="saved-search-term" required></textarea> </div> <div class="test-search-term-wrap"> <a href="#" class="try-search-term">Test search terms</a> </div> <div class="choice-group action-panel-extra-margin-top"> <span class="action-panel-label" id="fieldset-label"> Would you like email updates of new search results? </span> <fieldset id="saved-search-alert" aria-describedby="fieldset-label"> <legend class="usa-sr-only">Saved Search Alert Radio Buttons</legend> <ul class="radio-group-items"> <li> <input type="radio" id="saved-search-alert-yes" class="saved-search-alert-yes" name="saved-search-alert" value="yes" checked> <label for="saved-search-alert-yes" class="action-panel-label">Yes</label> </li> <li> <input aria-label="No radio input" type="radio" id="saved-search-alert-no" class="saved-search-alert-no" name="saved-search-alert" value="no"> <label for="saved-search-alert-no" class="action-panel-label">No</label> </li> </ul> </fieldset> </div> <div class="alert-schedule-wrap"> <div class="action-panel-control-wrap"> <label class="action-panel-label"> Email: </label> <span aria-label="Email address" id="saved-search-email" class="action-panel-label"><span class="action-panel-label-bold"></span> (<a class="myncbi-account-settings" href="https://www.ncbi.nlm.nih.gov/account/settings/">change</a>)</span> </div> <div class="action-panel-control-wrap action-panel-extra-margin-top"> <label for="saved-search-frequency" class="action-panel-label"> Frequency: </label> <select id="saved-search-frequency" class="no-border-panel-selector saved-search-frequency"> <option value="monthly">Monthly</option> <option value="weekly">Weekly</option> <option value="daily">Daily</option> </select> </div> <div class="action-panel-control-wrap saved-search-monthly-additional"> <label for="saved-search-monthly-on-day" class="action-panel-label"> Which day? </label> <select id="saved-search-monthly-on-day" class="no-border-panel-selector"> <option value="Sunday">The first Sunday</option> <option value="Monday">The first Monday</option> <option value="Tuesday">The first Tuesday</option> <option value="Wednesday">The first Wednesday</option> <option value="Thursday">The first Thursday</option> <option value="Friday">The first Friday</option> <option value="Saturday">The first Saturday</option> <option value="day">The first day</option> <option value="weekday">The first weekday</option> </select> </div> <div class="action-panel-control-wrap saved-search-weekly-additional"> <label for="saved-search-weekly-on-day" class="action-panel-label"> Which day? </label> <select id="saved-search-weekly-on-day" class="no-border-panel-selector saved-search-weekly-on-day"> <option value="Sunday">Sunday</option> <option value="Monday">Monday</option> <option value="Tuesday">Tuesday</option> <option value="Wednesday">Wednesday</option> <option value="Thursday">Thursday</option> <option value="Friday">Friday</option> <option value="Saturday">Saturday</option> </select> </div> <div class="action-panel-control-wrap"> <label for="saved-search-report" class="action-panel-label"> Report format: </label> <select id="saved-search-report" class="no-border-panel-selector saved-search-report"> <option value="DocSum">Summary</option> <option value="DocSumText">Summary (text)</option> <option value="Abstract">Abstract</option> <option value="AbstractText">Abstract (text)</option> <option value="MEDLINE">PubMed</option> </select> </div> <div class="action-panel-control-wrap"> <label for="saved-search-amount" class="action-panel-label"> Send at most: </label> <select id="saved-search-amount" class="no-border-panel-selector saved-search-amount"> <option value="1">1 item</option> <option value="5" selected>5 items</option> <option value="10">10 items</option> <option value="20">20 items</option> <option value="50">50 items</option> <option value="100">100 items</option> <option value="200">200 items</option> </select> </div> <div> <input type="checkbox" id="saved-search-send-if-no-result" class="saved-search-send-if-no-result" name="saved-search-send-if-no-result"> <label for="saved-search-send-if-no-result" class="action-panel-label smaller-checkbox"> Send even when there aren't any new results </label> </div> <div class="action-panel-control-wrap option-text-in-email-wrap"> <label for="saved-search-email-text" class="action-panel-label"> Optional text in email: </label> <textarea name="saved-search-email-text" id="saved-search-email-text" class="saved-search-email-text"></textarea> </div> </div> <div class="action-panel-actions"> <button class="action-panel-submit" type="submit" data-loading-label="Saving..." data-ga-category="save_share" data-ga-action="alert" data-ga-label="save"> Save </button> <button class="action-panel-cancel" aria-label="Close 'Your saved search' panel" ref="linksrc=close_saved_search_panel" aria-controls="saved-search-action-panel" aria-expanded="false" data-ga-category="save_share" data-ga-action="alert" data-ga-label="cancel"> Cancel </button> </div> </form> </div> </div> <div id="citation-manager-action-panel" class="citation-manager-action-panel action-panel" aria-hidden="true"> <div class="inner-wrap"> <h2 class="action-panel-heading"> Create a file for external citation management software </h2> <form id="citation-manager-action-panel-form" class="action-panel-content action-form" action="/results-export-ids/" data-by-search-action="/results-export-search-data/" data-by-ids-action="/results-export-ids/" method="post" data-by-search-method="post" data-by-ids-method="post"> <input type="hidden" name="csrfmiddlewaretoken" value="Sni8ogOUNwSfyfPovgvqqKpNKH96r3M98fT47VPtFSprCFdFnkog6SHQSm21VDgZ"> <input name="results-format" type="hidden" value="pubmed"/> <div class="action-panel-actions"> <button class="action-panel-submit" type="submit" data-loading-label="Sending..." data-ga-category="save_share" data-ga-action="citation_manager" data-ga-label="save"> Create file </button> <button class="action-panel-cancel" aria-label="Close 'Send citations to citation manager' panel" ref="linksrc=close_citation_manager_panel" aria-controls="citation-manager-action-panel" aria-expanded="false" data-ga-category="save_share" data-ga-action="citation_manager" data-ga-label="cancel"> Cancel </button> </div> </form> </div> </div> <div id="rss-action-panel" class="rss-action-panel action-panel " aria-hidden="true"> <div class="inner-wrap"> <h2 class="action-panel-heading"> Your RSS Feed </h2> <form id="rss-action-panel-form" class="rss-action-panel-form action-panel-content action-form" data-create-rss-feed-url="/create-rss-feed-url/" data-search-form-term-value=""> <input type="hidden" name="csrfmiddlewaretoken" value="Sni8ogOUNwSfyfPovgvqqKpNKH96r3M98fT47VPtFSprCFdFnkog6SHQSm21VDgZ"> <div class="action-panel-control-wrap"> <label for="rss-name" class="action-panel-label required-field-asterisk"> Name of RSS Feed: </label> <input maxlength="200" placeholder="Name" type="text" name="rss-name" id="rss-name" class="rss-name" value='' required pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/"> </div> <div class="rss-limit-wrap"> <div class="action-panel-control-wrap action-panel-extra-margin-top"> <label for="rss-limit" class="action-panel-label"> Number of items displayed: </label> <select id="rss-limit" class="no-border-panel-selector rss-limit"> <option value="5">5</option> <option value="10">10</option> <option value="15" selected="selected">15</option> <option value="20">20</option> <option value="50">50</option> <option value="100">100</option> </select> </div> </div> <div class="action-panel-actions"> <button class="action-panel-submit" type="submit" data-loading-label="Creating..." data-ga-category="save_share" data-ga-action="alert" data-ga-label="save"> Create RSS </button> <button class="action-panel-cancel" aria-label="Close 'Your RSS' panel" ref="linksrc=close_rss_panel" aria-controls="rss-action-panel" aria-expanded="false" data-ga-category="save_share" data-ga-action="alert" data-ga-label="cancel"> Cancel </button> </div> <div class="action-panel-control-wrap rss-link-copy-wrap"> <label for="rss-link" class="usa-sr-only">RSS Link</label> <input placeholder="Your RSS Feed Link" type="text" name="rss-link" id="rss-link" class="rss-link" title="RSS Link"> <button type="button" disabled class="rss-link-copy-button disabled" data-ga-category="save_share" data-ga-action="rss" data-ga-label="copy"> Copy </button> </div> </form> </div> </div> </div> </div> <div class="article-page" id="article-page" data-article-pmid="19801663"> <aside class="page-sidebar"> <div class="inner-wrap"> <div class="full-text-links"> <div class="full-view"> <h3 class="title"> Full text links </h3> <div class="full-text-links-list"> <a class="link-item dialog-focus" href="https://linkinghub.elsevier.com/retrieve/pii/S0021-9258(20)37702-4" target="_blank" rel="noopener" ref="linksrc=fulltextorjournal_fulltext&is_pmc=False&PrId=3048&itool=Abstract-def&log$=linkouticon&uid=19801663&db=pubmed&nlmid=2985121R" title="See full text options at Elsevier Science" data-ga-category="full_text" data-ga-action="Elsevier Science" data-ga-label="19801663" ><img src="https://cdn.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--linkinghub.elsevier.com-ihub-images-elsevieroa.png" alt="full text provider logo"><span class="text"> Elsevier Science </span></a><a class="link-item pmc " href="https://pmc.ncbi.nlm.nih.gov/articles/pmid/19801663/" target="_blank" rel="noopener" ref="linksrc=fulltextorjournal_fulltext&is_pmc=True&PrId=3494&itool=Abstract-def&log$=linkouticon&uid=19801663&db=pubmed&nlmid=2985121R" title="Free full text at PubMed Central" data-ga-category="full_text" data-ga-action="PMC" data-ga-label="19801663" ><span class="text"> Free PMC article </span></a> 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data-collections-open-dialog-enabled="false" data-collections-open-dialog-url="https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F19801663%2F%23open-collections-dialog" data-in-collections="false"><span class="button-label">Collections</span></button><div class="overlay" role="dialog"><div id="collections-action-dialog" class="dialog collections-dialog" aria-hidden="true"><div class="title">Add to Collections</div><div class="collections-action-panel action-panel"><form id="collections-action-dialog-form" class="collections-action-panel-form action-panel-content action-form action-panel-smaller-selectors" data-existing-collections-url="/list-existing-collections/" data-add-to-existing-collection-url="/add-to-existing-collection/" data-create-and-add-to-new-collection-url="/create-and-add-to-new-collection/" data-myncbi-max-collection-name-length="100" data-collections-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/"><input type="hidden" name="csrfmiddlewaretoken" value="Sni8ogOUNwSfyfPovgvqqKpNKH96r3M98fT47VPtFSprCFdFnkog6SHQSm21VDgZ"><div class="choice-group" role="radiogroup"><ul class="radio-group-items"><li><input type="radio" id="collections-action-dialog-new" class="collections-new" name="collections" value="new" data-ga-category="collections_button" data-ga-action="click" data-ga-label="collections_radio_new"><label for="collections-action-dialog-new">Create a new collection</label></li><li><input type="radio" id="collections-action-dialog-existing" class="collections-existing" name="collections" value="existing" checked="true" data-ga-category="collections_button" data-ga-action="click" data-ga-label="collections_radio_existing"><label for="collections-action-dialog-existing">Add to an existing collection</label></li></ul></div><div class="controls-wrapper"><div class="action-panel-control-wrap new-collections-controls"><label for="collections-action-dialog-add-to-new" class="action-panel-label required-field-asterisk"> Name your collection: </label><input type="text" name="add-to-new-collection" id="collections-action-dialog-add-to-new" class="collections-action-add-to-new" pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/" maxlength="100" data-ga-category="collections_button" data-ga-action="create_collection" data-ga-label="non_favorties_collection"><div class="collections-new-name-too-long usa-input-error-message selection-validation-message"> Name must be less than 100 characters </div></div><div class="action-panel-control-wrap existing-collections-controls"><label for="collections-action-dialog-add-to-existing" class="action-panel-label"> Choose a collection: </label><select id="collections-action-dialog-add-to-existing" class="action-panel-selector collections-action-add-to-existing" data-ga-category="collections_button" data-ga-action="select_collection" data-ga-label="($('.collections-action-add-to-existing').val() === 'Favorites') ? 'Favorites' : 'non_favorites_collection'"></select><div class="collections-retry-load-on-error usa-input-error-message selection-validation-message"> Unable to load your collection due to an error<br><a href="#">Please try again</a></div></div></div><div class="action-panel-actions"><button class="action-panel-submit" type="submit" data-loading-label="Adding..." data-pinger-ignore data-ga-category="collections_button" data-ga-action="click" data-ga-label="add"> Add </button><button class="action-panel-cancel" aria-label="Close 'Add to Collections' panel" ref="linksrc=close_collections_panel" aria-controls="collections-action-panel" aria-expanded="false" data-ga-category="collections_button" data-ga-action="click" data-ga-label="cancel"> Cancel </button></div></form></div></div></div></div><button class="more-actions-button more-actions-dialog-trigger" title="Open dialog with more actions to take" ref="linksrc=more_actions_btn"></button><div class="display-options" 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aria-label="Dropdown menu for journal The Journal of biological chemistry"><div class="title">Actions</div><div class="content"><ul class="journal-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22J+Biol+Chem%22%5Bjour%5D&sort=date&sort_order=desc" data-href="/?term=%22J+Biol+Chem%22%5Bjour%5D&sort=date&sort_order=desc" ref="linksrc=search_in_pubmed_journal_name_link&journal_abbrev=J Biol Chem" data-ga-category="search" data-ga-action="journal_link" data-ga-label="J Biol Chem"> Search in PubMed </a></li><li><a class="search-in-nlm-catalog-link dropdown-block-link" ref ="linksrc=search_in_nlm_catalog_link" href="https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22J+Biol+Chem%22%5BTitle+Abbreviation%5D" data-ga-category="search_catalog" data-ga-action="journal_link" data-ga-label="J Biol Chem"> Search in NLM Catalog </a></li><li><a class="add-to-search-link dropdown-block-link" ref ="linksrc=add_to_search_link" role="button" data-search-term='"J Biol Chem"[jour]' data-ga-category="search" data-ga-action="add_to_search" data-ga-label='"J Biol Chem"[jour]' href="#"> Add to Search </a></li></ul></div></div></div><span class="period">. </span><span class="cit">2009 Dec 4;284(49):34211-22.</span> </div> <span class="citation-doi"> doi: 10.1074/jbc.M109.041152. </span> <span class="secondary-date"> Epub 2009 Sep 30. </span> </div> <h1 class="heading-title"> Microenvironmental pH is a key factor for exosome traffic in tumor cells </h1> <div class="inline-authors"> <div class="authors"> <div class="authors-list"> <span class="authors-list-item "><a class="full-name" href="/?term=Parolini+I&cauthor_id=19801663" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Isabella Parolini">Isabella Parolini</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Hematology, Istituto Superiore di Sanità, Rome 00161, Italy." href="#full-view-affiliation-1" ref="linksrc=author_aff"> 1 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Federici+C&cauthor_id=19801663" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Cristina Federici">Cristina Federici</a><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Raggi+C&cauthor_id=19801663" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Carla Raggi">Carla Raggi</a><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Lugini+L&cauthor_id=19801663" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Luana Lugini">Luana Lugini</a><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Palleschi+S&cauthor_id=19801663" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Simonetta Palleschi">Simonetta Palleschi</a><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=De+Milito+A&cauthor_id=19801663" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Angelo De Milito">Angelo De Milito</a><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Coscia+C&cauthor_id=19801663" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Carolina Coscia">Carolina Coscia</a><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Iessi+E&cauthor_id=19801663" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Elisabetta Iessi">Elisabetta Iessi</a><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Logozzi+M&cauthor_id=19801663" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Mariantonia Logozzi">Mariantonia Logozzi</a><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Molinari+A&cauthor_id=19801663" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Agnese Molinari">Agnese Molinari</a><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Colone+M&cauthor_id=19801663" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Marisa Colone">Marisa Colone</a><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Tatti+M&cauthor_id=19801663" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Massimo Tatti">Massimo Tatti</a><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Sargiacomo+M&cauthor_id=19801663" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Massimo Sargiacomo">Massimo Sargiacomo</a><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Fais+S&cauthor_id=19801663" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Stefano Fais">Stefano Fais</a></span> </div> </div> </div> <div class="short-article-details"> Affiliations <button class="more-details" id="toggle-authors" data-alt-text="Collapse" aria-controls="expanded-authors" aria-expanded="false" data-pinger-ignore data-fetch-url="/19801663/long-authors/" data-id-prefix=""> <span class="title"> Expand </span> </button> </div> <div 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doi"> <span class="id-label"> DOI: </span> <a class="id-link" target="_blank" rel="noopener" ref="linksrc=article_id_link&article_id=10.1074/jbc.M109.041152&id_type=DOI" href="https://doi.org/10.1074/jbc.m109.041152" data-ga-category="full_text" data-ga-action="DOI" > 10.1074/jbc.M109.041152 </a> </span> </li> </ul> <div class="in-clipboard-label " hidden> Item in Clipboard </div> </div> <div class="short-view" id="short-view-heading"> <h1 class="heading-title"> Microenvironmental pH is a key factor for exosome traffic in tumor cells </h1> <div class="short-citation"> <span class="authors-list"> <span class="authors-list-item "><span class="full-name">Isabella Parolini</span><span class="citation-separator"> et al.</span></span> </span> <span class="citation-journal"> J Biol Chem<span class="citation-separator">.</span> </span> <span class="date"> <time class="citation-year" datetime="2009">2009</time><span class="citation-separator">.</span> </span> </div> <div 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class="cit">2009 Dec 4;284(49):34211-22.</span> </div> <span class="citation-doi"> doi: 10.1074/jbc.M109.041152. </span> <span class="secondary-date"> Epub 2009 Sep 30. </span> </div> <div class="expanded-authors" id="short-view-expanded-authors"> <div class="authors"> <h3 class="title"> Authors </h3> <div class="authors-list"> <span class="authors-list-item "><a class="full-name" href="/?term=Parolini+I&cauthor_id=19801663" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Isabella Parolini">Isabella Parolini</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Hematology, Istituto Superiore di Sanità, Rome 00161, Italy." href="#short-view-affiliation-1" ref="linksrc=author_aff"> 1 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Federici+C&cauthor_id=19801663" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Cristina Federici">Cristina Federici</a><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Raggi+C&cauthor_id=19801663" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Carla Raggi">Carla Raggi</a><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Lugini+L&cauthor_id=19801663" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Luana Lugini">Luana Lugini</a><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Palleschi+S&cauthor_id=19801663" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Simonetta Palleschi">Simonetta Palleschi</a><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=De+Milito+A&cauthor_id=19801663" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Angelo De Milito">Angelo De Milito</a><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Coscia+C&cauthor_id=19801663" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Carolina Coscia">Carolina Coscia</a><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Iessi+E&cauthor_id=19801663" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Elisabetta Iessi">Elisabetta Iessi</a><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Logozzi+M&cauthor_id=19801663" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Mariantonia Logozzi">Mariantonia Logozzi</a><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Molinari+A&cauthor_id=19801663" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Agnese Molinari">Agnese Molinari</a><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Colone+M&cauthor_id=19801663" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Marisa Colone">Marisa Colone</a><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Tatti+M&cauthor_id=19801663" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Massimo Tatti">Massimo Tatti</a><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Sargiacomo+M&cauthor_id=19801663" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Massimo Sargiacomo">Massimo Sargiacomo</a><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Fais+S&cauthor_id=19801663" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Stefano Fais">Stefano Fais</a></span> </div> </div> <div class="affiliations"> <h3 class="title"> Affiliation </h3> <ul class="item-list"> <li data-affiliation-id="short-view-affiliation-1" id="short-view-affiliation-1" ><sup class="key">1</sup> Department of Hematology, Istituto Superiore di Sanità, Rome 00161, Italy.</li> </ul> </div> </div> <ul class="identifiers" id="short-view-identifiers"> <li> <span class="identifier pubmed"> <span class="id-label"> PMID: </span> <strong class="current-id" title="PubMed ID">19801663</strong> </span> </li> <li> <span class="identifier pmc"> <span class="id-label"> PMCID: </span> <a class="id-link" target="_blank" rel="noopener" ref="linksrc=article_id_link&article_id=PMC2797191&id_type=PMC" href="https://pmc.ncbi.nlm.nih.gov/articles/PMC2797191/" data-ga-category="full_text" data-ga-action="PMCID" > PMC2797191 </a> </span> </li> <li> <span class="identifier doi"> <span class="id-label"> DOI: </span> <a class="id-link" target="_blank" rel="noopener" ref="linksrc=article_id_link&article_id=10.1074/jbc.M109.041152&id_type=DOI" href="https://doi.org/10.1074/jbc.m109.041152" data-ga-category="full_text" data-ga-action="DOI" > 10.1074/jbc.M109.041152 </a> </span> </li> </ul> <div class="in-clipboard-label " hidden> Item in Clipboard </div> </div> </div> </header> <div class="actions-buttons inline"><div class="inner-wrap"><button class="full-text-links-button full-text-links-dialog-trigger" title="Open dialog with full text links" ref="linksrc=full_text_links"> Full text links </button><button class="citation-button citation-dialog-trigger" aria-label="Open dialog with citation text in different styles" data-ga-category="save_share" data-ga-action="cite" data-ga-label="open" data-all-citations-url="/19801663/citations/" data-citation-style="nlm" data-pubmed-format-link="/19801663/export/"><span class="button-label">Cite</span></button><button class="more-actions-button more-actions-dialog-trigger" title="Open dialog with more actions to take" ref="linksrc=more_actions_btn"></button><div class="display-options" data-format-key="format" data-default-format-value="abstract" data-current-format-value="abstract" role="region"><button class="trigger usa-button" title="Change format" data-ga-category="display_options" data-ga-action="display_options_dialog"><span class="button-label">Display options</span></button><div class="dropdown" hidden><div class="title"> Display options </div><div class="content"><div class="format-container"><span class="option-label"> Format </span><select name="format" data-initial-value="abstract" aria-label="Display format" id="inline-actions-display-format"><option value="abstract">Abstract</option><option value="pubmed">PubMed</option><option value="pmid">PMID</option></select></div></div></div></div></div></div> <div class="abstract" id="abstract"> <h2 class="title"> Abstract </h2> <div class="abstract-content selected" id="eng-abstract"> <p> Exosomes secreted by normal and cancer cells carry and deliver a variety of molecules. To date, mechanisms referring to tumor exosome trafficking, including release and cell-cell transmission, have not been described. To gain insight into this, exosomes purified from metastatic melanoma cell medium were labeled with a lipid fluorescent probe, R18, and analyzed by spectrofluorometry and confocal microscopy. A low pH condition is a hallmark of tumor malignancy, potentially influencing exosome release and uptake by cancer cells. Using different pH conditions as a modifier of exosome traffic, we showed (i) an increased exosome release and uptake at low pH when compared with a buffered condition and (ii) exosome uptake by melanoma cells occurred by fusion. Membrane biophysical analysis, such as fluidity and lipid composition, indicated a high rigidity and sphingomyelin/ganglioside GM3 (N-acetylneuraminylgalactosylglucosylceramide) content in exosomes released at low pH. This was likely responsible for the increased fusion efficiency. Consistent with these results, pretreatment with proton pump inhibitors led to an inhibition of exosome uptake by melanoma cells. Fusion efficiency of tumor exosomes resulted in being higher in cells of metastatic origin than in those derived from primary tumors or normal cells. Furthermore, we found that caveolin-1, a protein involved in melanoma progression, is highly delivered through exosomes released in an acidic condition. The results of our study provide the evidence that exosomes may be used as a delivery system for paracrine diffusion of tumor malignancy, in turn supporting the importance of both exosomes and tumor pH as key targets for future anti-cancer strategies. </p> </div> </div> <p class="disclaimer" id="disclaimer"> <a href="/disclaimer/" target="_blank" ga_category="literature_resources" ga_action="disclaimer_link" ga_label="under_abstract">PubMed Disclaimer</a> </p> <div class="figures" id="figures"> <h2 class="title"> Figures </h2> <div class="figures-list" id="slides-container" itemscope itemtype="http://schema.org/ImageGallery"> <figure class="figure-item " itemscope itemtype="http://schema.org/ImageObject" itemprop="associatedMedia" data-slide-index="0" data-label-slug="figure-1"> <a class="figure-link" href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/85ee/2797191/321ac2dc547b/zbc0520997020001.jpg" itemprop="contentUrl" aria-describedby="figure-caption-0" role="button" data-image-width="520" data-image-height="1294" data-image-alt="FIGURE 1." data-pmc-id="PMC2797191" data-figure-id="F1"> <img class="figure-thumb" itemprop="thumbnail" id="article-image-0" src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/85ee/2797191/d7c523c5acf0/zbc0520997020001.gif" alt="FIGURE 1." /> </a> <meta itemprop="width" itemtype="http://schema.org/ImageObject" content="520"> <meta itemprop="height" itemtype="http://schema.org/ImageObject" content="1294"> <div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true"> <div class="caption-wrap"> <strong class="figure-label"> <p> FIGURE 1. </p> </strong> <div class="figure-caption-contents"><b> Exosome release in acidic and… </b></div> </div> </div> <div class="figure-caption-medium figure-caption-text" aria-hidden="true"> <strong class="figure-label"> <p> FIGURE 1. </p> </strong> <div class="figure-caption-contents"><b> Exosome release in acidic and buffered pH conditions. </b> <i> A </i> , exosomes (100 μg)…</div> </div> <figcaption id="figure-caption-0" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description"> <strong class="figure-label"> FIGURE 1. </strong> <div class="figure-caption-contents"><b>Exosome release in acidic and buffered pH conditions.</b> <i>A</i>, exosomes (100 μg) isolated from Mel1 cells culture medium were NHS-biotin-labeled and loaded on a 10–60% continuous sucrose gradient. Eleven fractions were analyzed by Western blotting with horseradish peroxidase-streptavidin. Results indicate a molecules profile with molecular mass ranging between 97 and 21 kDa enriched in fractions 3–6 corresponding to density 1.11–1.17 g/ml. These fractions were also found positive for exosome markers such as Lamp-2, CD81, and Rab 5B by Western blotting. <i>B</i>, Mel1 cells (3 × 10<sup>6</sup> cell/ml) were cultured in buffered (pH 7.4) or acidic (pH 6.0) media. At the indicated days exosomes were isolated, quantified by protein assay, and normalized on 1 × 10<sup>6</sup> viable cells. <i>Points</i>, means (<i>n</i> = 4); <i>bars</i>, S.D. *, <i>p</i> < 0.05. <i>C</i>, Western blotting of Lamp-2 and Rab 5B in exoMel1<sub>ac</sub> and exoMel1 released from parental cells at 2, 3, and 4 days. Note that Lamp-2 and Rab 5B expressions increased with time in the acidic exosomes. A representative Western blotting of three independent experiments is shown.</div> </figcaption> </figure> <figure class="figure-item " itemscope itemtype="http://schema.org/ImageObject" itemprop="associatedMedia" data-slide-index="1" data-label-slug="figure-2"> <a class="figure-link" href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/85ee/2797191/bb2406e82ee9/zbc0520997020002.jpg" itemprop="contentUrl" aria-describedby="figure-caption-1" role="button" data-image-width="514" data-image-height="647" data-image-alt="FIGURE 2." data-pmc-id="PMC2797191" data-figure-id="F2"> <img class="figure-thumb" itemprop="thumbnail" id="article-image-1" src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/85ee/2797191/806a20990714/zbc0520997020002.gif" alt="FIGURE 2." /> </a> <meta itemprop="width" itemtype="http://schema.org/ImageObject" content="514"> <meta itemprop="height" itemtype="http://schema.org/ImageObject" content="647"> <div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true"> <div class="caption-wrap"> <strong class="figure-label"> <p> FIGURE 2. </p> </strong> <div class="figure-caption-contents"><b> Exosome fusion with parental cells.… </b></div> </div> </div> <div class="figure-caption-medium figure-caption-text" aria-hidden="true"> <strong class="figure-label"> <p> FIGURE 2. </p> </strong> <div class="figure-caption-contents"><b> Exosome fusion with parental cells. </b> <i> A </i> , a panel of confocal laser-scanning microscopy…</div> </div> <figcaption id="figure-caption-1" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description"> <strong class="figure-label"> FIGURE 2. </strong> <div class="figure-caption-contents"><b>Exosome fusion with parental cells.</b> <i>A</i>, a panel of confocal laser-scanning microscopy images of a human metastatic melanoma is shown. NHS-rhodamine-labeled exosomes (<i>red</i>) were incubated with cells for 4 h followed by fixation and labeling with green fluorescent antibodies directed to Rab 5B (early endosomes), Lamp-1 (lysosomes), and Golgina (Golgi apparatus). <i>Arrows</i> indicate the events of colocalization (<i>yellow</i>) in all samples, with the exception of Golgi compartment. Images in the <i>right column</i> represent magnification of the images on the <i>left column. Bars</i>: <i>left panels</i>, 10 μm; <i>right panels</i>, 4 μm. <i>B</i>, R18-exoMel1 were left untreated or mixed with 1 × 10<sup>6</sup> Mel1 cells. Note that a fluorescence dequenching (<i>FD</i>) curve was observed only after the addition of the cells. <i>Tx 100</i>, Triton X-100. <i>C</i>, R18-exoMel1 were left untreated or pretreated with 0.5% PAF before the addition to Mel1 cells, and fusion activity was tested. A representative fluorescence dequenching curve is shown. <i>Inset</i>, statistical analysis obtained by 20 min of kinetic experiments is shown. Values are the means ± S.D. <i><sup>a</sup></i> = <i>p</i> < 0.05 <i>versus</i> control (<i>n</i> = 3). <i>D</i>, Mel1 cells (1 × 10<sup>6</sup>) were left untreated or treated with filipin, then subjected to a fusion test with R18-exoMel1. A representative fluorescence dequenching curve is shown. <i>Inset</i>, statistical analysis obtained by 30 min kinetic experiments is shown. Values are the means ± S.D. <i><sup>a</sup></i> = <i>p</i> < 0.01 <i>versus</i> control (<i>n</i> = 3). <i>E</i>, R18-exoMel1<sub>ac</sub> and R18-exoMel1 (10 μg) were mixed with parental cells at the corresponding pH, and fusion was monitored. A representative fluorescence dequenching curve is shown. Statistical analysis on 5-, 20-, and 30-min kinetic experiments is represented. Values are the means ± S.D. <i><sup>a</sup></i>, <i>p</i> < 0.05 (<i>n</i> = 3). <i>F</i>, streptavidin blotting is shown. 20 μg of biotinylated exosomes were incubated with parental cells (1 × 10<sup>6</sup>) at the corresponding pH (<i>lane 1</i>, exoMel1 on Mel1; <i>lane 2</i>, exoMel1<sub>ac</sub> on Mel1<sub>ac</sub>) or with filipin-treated cells (<i>lane 3</i>, exoMel1 on Mel1; <i>lane 4</i>, exoMel1<sub>ac</sub> on Mel1<sub>ac</sub>) for 1 h at 37 °C. Immunoblotting of nucleolin protein expression represents a control for protein equal loading. A representative Western blot of three independent experiments is shown. Numbers expressed in arbitrary units (<i>a.u</i>.) represent streptavidin densitometry analysis.</div> </figcaption> </figure> <figure class="figure-item " itemscope itemtype="http://schema.org/ImageObject" itemprop="associatedMedia" data-slide-index="2" data-label-slug="figure-3"> <a class="figure-link" href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/85ee/2797191/ba958bcb2aec/zbc0520997020003.jpg" itemprop="contentUrl" aria-describedby="figure-caption-2" role="button" data-image-width="479" data-image-height="356" data-image-alt="FIGURE 3." data-pmc-id="PMC2797191" data-figure-id="F3"> <img class="figure-thumb" itemprop="thumbnail" id="article-image-2" src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/85ee/2797191/927f7a3b1405/zbc0520997020003.gif" alt="FIGURE 3." /> </a> <meta itemprop="width" itemtype="http://schema.org/ImageObject" content="479"> <meta itemprop="height" itemtype="http://schema.org/ImageObject" content="356"> <div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true"> <div class="caption-wrap"> <strong class="figure-label"> <p> FIGURE 3. </p> </strong> <div class="figure-caption-contents"><b> <i> In vivo </i> exosome/melanoma lipids colocalization… </b></div> </div> </div> <div class="figure-caption-medium figure-caption-text" aria-hidden="true"> <strong class="figure-label"> <p> FIGURE 3. </p> </strong> <div class="figure-caption-contents"><b> <i> In vivo </i> exosome/melanoma lipids colocalization analysis through confocal laser-scanning microscopy. </b> The panel shows…</div> </div> <figcaption id="figure-caption-2" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description"> <strong class="figure-label"> FIGURE 3. </strong> <div class="figure-caption-contents"><b><i>In vivo</i> exosome/melanoma lipids colocalization analysis through confocal laser-scanning microscopy.</b> The panel shows three different fields (<i>A</i>, <i>B</i>, and <i>C</i>) of unfixed cell cultures in which co-cultivation of R18-labeled exosomes (<i>red</i>, magnifications in <i>A1</i>, <i>B1</i>, <i>C1</i>) and PKH67-labeled cells (<i>green</i>, magnifications in <i>A2</i>, <i>B2</i>, <i>C2</i>) is analyzed. In particular, <i>arrows</i> in <i>A1</i>, <i>B1</i>, and <i>C1</i> images indicate free exosomes in cell culture medium not yet interacting with the cells. The <i>yellow points</i> (<i>A</i>, <i>B</i>, and <i>C</i> and <i>arrows</i> in magnification <i>A3</i>, <i>B3</i>, and <i>C3</i>) correspond to cell/exosome lipid mixing events, both at plasma membrane and intracellular levels. <i>Bars</i>: <i>A</i>, 48 μm; <i>B</i>, 46 μm; <i>C</i>, 42 μm; <i>A</i>3, 20 μm; <i>B</i>3, 24 μm; <i>C</i>3, 13 μm.</div> </figcaption> </figure> <figure class="figure-item " itemscope itemtype="http://schema.org/ImageObject" itemprop="associatedMedia" data-slide-index="3" data-label-slug="figure-4"> <a class="figure-link" href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/85ee/2797191/9be9917bfdbe/zbc0520997020004.jpg" itemprop="contentUrl" aria-describedby="figure-caption-3" role="button" data-image-width="520" data-image-height="693" data-image-alt="FIGURE 4." data-pmc-id="PMC2797191" data-figure-id="F4"> <img class="figure-thumb" itemprop="thumbnail" id="article-image-3" src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/85ee/2797191/e216ba0b7ca3/zbc0520997020004.gif" alt="FIGURE 4." /> </a> <meta itemprop="width" itemtype="http://schema.org/ImageObject" content="520"> <meta itemprop="height" itemtype="http://schema.org/ImageObject" content="693"> <div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true"> <div class="caption-wrap"> <strong class="figure-label"> <p> FIGURE 4. </p> </strong> <div class="figure-caption-contents"><b> Exosomes and parental cells membrane… </b></div> </div> </div> <div class="figure-caption-medium figure-caption-text" aria-hidden="true"> <strong class="figure-label"> <p> FIGURE 4. </p> </strong> <div class="figure-caption-contents"><b> Exosomes and parental cells membrane fluidity and lipid phase state at different pH… </b></div> </div> <figcaption id="figure-caption-3" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description"> <strong class="figure-label"> FIGURE 4. </strong> <div class="figure-caption-contents"><b>Exosomes and parental cells membrane fluidity and lipid phase state at different pH conditions.</b> <i>A</i>, shown are Laurdan GP values (340-nm excitation wavelength; 37 °C) of buffered and acidic Mel1 cells (<i>open bars</i>) and exoMel1 and exoMel1<sub>ac</sub> (<i>filled bars</i>). The higher GP values of exosomes indicate a higher rigidity of such membranes with respect to bulk of the cellular membranes. ExoMel1<sub>ac</sub> are significantly more rigid than exoMel1. Data are the means ± S.E. of at least three independent experiments. *, <i>p</i> < 0.05 <i>versus</i> the corresponding bulk cellular membranes. <i>B</i>, Laurdan excitation GP spectra of Mel1 (<i>a, filled triangles</i>), Mel1<sub>ac</sub> cells (<i>b, filled circles</i>), exoMel1 (<i>c, open triangles</i>), and exoMel1<sub>ac</sub> (<i>d, open circles</i>) at 37 °C. Laurdan GP values decrease by increasing excitation wavelength, indicating that both cell and exosome membranes are in a liquid-crystalline lipid phase in the absence of coexisting gel-phase lipid domains. The curves are representatives of three consistent experiments.</div> </figcaption> </figure> <figure class="figure-item " itemscope itemtype="http://schema.org/ImageObject" itemprop="associatedMedia" data-slide-index="4" data-label-slug="figure-5"> <a class="figure-link" href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/85ee/2797191/2fd9d716be48/zbc0520997020005.jpg" itemprop="contentUrl" aria-describedby="figure-caption-4" role="button" data-image-width="514" data-image-height="443" data-image-alt="FIGURE 5." data-pmc-id="PMC2797191" data-figure-id="F5"> <img class="figure-thumb" itemprop="thumbnail" id="article-image-4" src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/85ee/2797191/b448a2456ae4/zbc0520997020005.gif" alt="FIGURE 5." /> </a> <meta itemprop="width" itemtype="http://schema.org/ImageObject" content="514"> <meta itemprop="height" itemtype="http://schema.org/ImageObject" content="443"> <div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true"> <div class="caption-wrap"> <strong class="figure-label"> <p> FIGURE 5. </p> </strong> <div class="figure-caption-contents"><b> Role of microenvironmental pH in… </b></div> </div> </div> <div class="figure-caption-medium figure-caption-text" aria-hidden="true"> <strong class="figure-label"> <p> FIGURE 5. </p> </strong> <div class="figure-caption-contents"><b> Role of microenvironmental pH in exosome fusion. </b> <i> A </i> , R18-exoMel1 and R18-exoMel1 <sub> ac… </sub></div> </div> <figcaption id="figure-caption-4" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description"> <strong class="figure-label"> FIGURE 5. </strong> <div class="figure-caption-contents"><b>Role of microenvironmental pH in exosome fusion.</b> <i>A</i>, R18-exoMel1 and R18-exoMel1<sub>ac</sub> were mixed with both acidic and buffered Mel1 cells (1 × 10<sup>6</sup>), and fusion efficiency was tested for 30 min. <i>Points</i>, means ± S.D. <i>FD</i>, fluorescence dequenching. <i>B</i>, NHS-biotin-buffered (pH 7.4) or acidic (pH 6.0) exosomes (25 μg) were incubated for 1 h with untreated or PPI-treated parental cells, then cells were analyzed by streptavidin blotting. Western blotting of nucleolin represents a control for cell protein equal loading. <i>Numbers</i> represent the whole lane densitometry analysis expressed in arbitrary units (<i>a.u</i>.). <i>Points</i>, means ± S.D. <i><sup>a</sup> p</i> < 0.01 <i>versus</i> control (pH 6.0) (<i>n</i> = 3). <i>C</i>, R18-exoMel1 were added to metastatic melanoma (Mel1–3), primary melanoma (MelP1–3), and normal donor-derived PBMC, and fusion efficiency was tested for 30 min. <i>Points</i>, means ± S.D., (<i>n</i> = 3). <i>D</i>, R18-exoMel1 (<i>red</i>) were incubated for 3 h with PKH67-PBMC (<i>green</i>) and analyzed by confocal laser-scanning microscopy. The image clearly shows the absence of lipid colocalization areas. The rare event of colocalization observed in PBMC cells is likely due to the presence of monocytes, as recognizable from nuclear morphology. <i>Bar</i>, 20 μm.</div> </figcaption> </figure> <figure class="figure-item " itemscope itemtype="http://schema.org/ImageObject" itemprop="associatedMedia" data-slide-index="5" data-label-slug="figure-6"> <a class="figure-link" href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/85ee/2797191/844c5c4d2ee4/zbc0520997020006.jpg" itemprop="contentUrl" aria-describedby="figure-caption-5" role="button" data-image-width="520" data-image-height="760" data-image-alt="FIGURE 6." data-pmc-id="PMC2797191" data-figure-id="F6"> <img class="figure-thumb" itemprop="thumbnail" id="article-image-5" src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/85ee/2797191/cf70daae6309/zbc0520997020006.gif" alt="FIGURE 6." /> </a> <meta itemprop="width" itemtype="http://schema.org/ImageObject" content="520"> <meta itemprop="height" itemtype="http://schema.org/ImageObject" content="760"> <div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true"> <div class="caption-wrap"> <strong class="figure-label"> <p> FIGURE 6. </p> </strong> <div class="figure-caption-contents"><b> Exosomes delivery of cav-1. </b> <i> A… </i></div> </div> </div> <div class="figure-caption-medium figure-caption-text" aria-hidden="true"> <strong class="figure-label"> <p> FIGURE 6. </p> </strong> <div class="figure-caption-contents"><b> Exosomes delivery of cav-1. </b> <i> A </i> , R18-exoMe665/1 <sub> ac </sub> and R18-exoMe665/1 (10 μg) were…</div> </div> <figcaption id="figure-caption-5" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description"> <strong class="figure-label"> FIGURE 6. </strong> <div class="figure-caption-contents"><b>Exosomes delivery of cav-1.</b> <i>A</i>, R18-exoMe665/1<sub>ac</sub> and R18-exoMe665/1 (10 μg) were mixed with parental cells at the corresponding pH and fusion monitored. A representative fluorescence dequenching (<i>FD</i>) curve is shown. <i>B</i>, cav-1 and Lamp-2 immunoblotting on WM983A cell membranes after incubation with exoMe665/1 and exoMe665/1<sub>ac</sub>. <i>Control</i> represents WM983A membranes in the absence of exoMe665/1 incubation. A representative Western blot of two independent experiments is shown.</div> </figcaption> </figure> </div> <!-- Root element of PhotoSwipe. Must have class pswp. --> <div class="pswp figures-dialog" id="figures-dialog" tabindex="-1" role="dialog" aria-hidden="true" data-image-gallery-uid="article-figures" aria-label="Figures Dialog"> <!-- Background of PhotoSwipe. It's a separate element as animating opacity is faster than rgba(). --> <div class="pswp__bg"></div> <!-- Slides wrapper with overflow:hidden. --> <div class="pswp__scroll-wrap"> <!-- Container that holds slides. PhotoSwipe keeps only 3 of them in the DOM to save memory. 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ref="linksrc=add_to_search_link" role="button" data-search-term=""Neoplasm Metastasis"[MeSH]" data-ga-category="search" data-ga-action="add_to_search" data-ga-label=""Neoplasm Metastasis"[MeSH]" href="#"> Add to Search </a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link" aria-label="Toggle dropdown menu for keyword Protons" tabindex="0" aria-controls="keyword-actions-mesh-terms-13" aria-expanded="false" data-pinger-ignore> Protons </button><div id="keyword-actions-mesh-terms-13" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword Protons"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22Protons%22%5BMeSH%5D&sort=date&sort_order=desc" data-href="/?term=%22Protons%22%5BMeSH%5D&sort=date&sort_order=desc" 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Neoplasms / metabolism </button><div id="keyword-actions-mesh-terms-14" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword Skin Neoplasms / metabolism"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22Skin+Neoplasms%2Fmetabolism%22%5BMeSH%5D&sort=date&sort_order=desc" data-href="/?term=%22Skin+Neoplasms%2Fmetabolism%22%5BMeSH%5D&sort=date&sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&mesh="Skin Neoplasms/metabolism"[MeSH]" data-ga-category="search" data-ga-action="mesh_term" data-ga-label="Skin Neoplasms / metabolism"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=Skin+Neoplasms" data-ga-category="search_mesh" data-ga-action="mesh_term_link" data-ga-label="Skin Neoplasms / metabolism"> Search in MeSH </a></li><li><a class="add-to-search-link dropdown-block-link" ref="linksrc=add_to_search_link" role="button" data-search-term=""Skin Neoplasms/metabolism"[MeSH]" data-ga-category="search" data-ga-action="add_to_search" data-ga-label=""Skin Neoplasms/metabolism"[MeSH]" href="#"> Add to Search </a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link" aria-label="Toggle dropdown menu for keyword Skin Neoplasms / pathology" tabindex="0" aria-controls="keyword-actions-mesh-terms-15" aria-expanded="false" data-pinger-ignore> Skin Neoplasms / pathology </button><div id="keyword-actions-mesh-terms-15" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword Skin Neoplasms / pathology"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22Skin+Neoplasms%2Fpathology%22%5BMeSH%5D&sort=date&sort_order=desc" data-href="/?term=%22Skin+Neoplasms%2Fpathology%22%5BMeSH%5D&sort=date&sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&mesh="Skin Neoplasms/pathology"[MeSH]" data-ga-category="search" data-ga-action="mesh_term" data-ga-label="Skin Neoplasms / pathology"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=Skin+Neoplasms" data-ga-category="search_mesh" data-ga-action="mesh_term_link" data-ga-label="Skin Neoplasms / pathology"> Search in MeSH </a></li><li><a class="add-to-search-link dropdown-block-link" ref="linksrc=add_to_search_link" role="button" data-search-term=""Skin Neoplasms/pathology"[MeSH]" data-ga-category="search" data-ga-action="add_to_search" data-ga-label=""Skin Neoplasms/pathology"[MeSH]" href="#"> Add to Search </a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link" aria-label="Toggle dropdown menu for keyword Spectrometry, Fluorescence / methods" tabindex="0" aria-controls="keyword-actions-mesh-terms-16" aria-expanded="false" data-pinger-ignore> Spectrometry, Fluorescence / methods </button><div id="keyword-actions-mesh-terms-16" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword Spectrometry, Fluorescence / methods"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22Spectrometry%2C+Fluorescence%2Fmethods%22%5BMeSH%5D&sort=date&sort_order=desc" data-href="/?term=%22Spectrometry%2C+Fluorescence%2Fmethods%22%5BMeSH%5D&sort=date&sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&mesh="Spectrometry, Fluorescence/methods"[MeSH]" data-ga-category="search" data-ga-action="mesh_term" 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