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<!DOCTYPE html> <html lang="en" class="no-js"> <head> <meta charset="UTF-8"> <meta http-equiv="X-UA-Compatible" content="IE=edge"> <meta name="applicable-device" content="pc,mobile"> <meta name="viewport" content="width=device-width, initial-scale=1"> <meta name="robots" content="max-image-preview:large"> <meta name="access" content="No"> <meta name="360-site-verification" content="1268d79b5e96aecf3ff2a7dac04ad990" /> <title>Epithelial-mesenchymal plasticity in circulating tumor cells | Journal of Molecular Medicine</title> <meta name="twitter:site" content="@SpringerLink"/> <meta name="twitter:card" content="summary_large_image"/> <meta name="twitter:image:alt" content="Content cover image"/> <meta name="twitter:title" content="Epithelial-mesenchymal plasticity in circulating tumor cells"/> <meta name="twitter:description" content="Journal of Molecular Medicine - Epithelial-to-Mesenchymal Transition (EMT) is a complex process that supports the migratory capacity of epithelial tumor cells and is thought to play a crucial role..."/> <meta name="twitter:image" content="https://static-content.springer.com/image/art%3A10.1007%2Fs00109-016-1500-6/MediaObjects/109_2016_1500_Fig1_HTML.gif"/> <meta name="journal_id" content="109"/> <meta name="dc.title" content="Epithelial-mesenchymal plasticity in circulating tumor cells"/> <meta name="dc.source" content="Journal of Molecular Medicine 2016 95:2"/> <meta name="dc.format" content="text/html"/> <meta name="dc.publisher" content="Springer"/> <meta name="dc.date" content="2016-12-24"/> <meta name="dc.type" content="ReviewPaper"/> <meta name="dc.language" content="En"/> <meta name="dc.copyright" content="2016 Springer-Verlag Berlin Heidelberg"/> <meta name="dc.rights" content="2016 Springer-Verlag Berlin Heidelberg"/> <meta name="dc.rightsAgent" content="journalpermissions@springernature.com"/> <meta name="dc.description" content="Epithelial-to-Mesenchymal Transition (EMT) is a complex process that supports the migratory capacity of epithelial tumor cells and is thought to play a crucial role in promoting cancer metastasis. Despite the wealth of experimental data, the exact role of EMT in cancer patients remains more controversial. Over the past 10&nbsp;years, sensitive technologies that allow the detection and molecular characterization of circulating tumor cells (CTCs) in the peripheral blood of tumor patients have been developed. These analyses help to shed new light into the importance of EMT for human tumor cell dissemination. CTCs with mesenchymal features can be attributed in some clinical studies (in particularly on breast cancer) to higher disease stages, presence of metastases, and even to therapy response and worse outcome. However, the published studies addressing the impact of mesenchymal-like CTCs show heterogeneity with regard to assay specificity, size of cancer and control groups, and endpoint parameters. In the present review, we present the key features of the biology of CTCs in relation to epithelial-to-mesenchy-mal plasticity, describe the current technologies for enrichment and detection of CTCs with high epithelial-mesenchymal plasticity, and discuss the clinical studies that have assessed the relevance of mesenchymal CTCs in carcinoma patients."/> <meta name="prism.issn" content="1432-1440"/> <meta name="prism.publicationName" content="Journal of Molecular Medicine"/> <meta name="prism.publicationDate" content="2016-12-24"/> <meta name="prism.volume" content="95"/> <meta name="prism.number" content="2"/> <meta name="prism.section" content="ReviewPaper"/> <meta name="prism.startingPage" content="133"/> <meta name="prism.endingPage" content="142"/> <meta name="prism.copyright" content="2016 Springer-Verlag Berlin Heidelberg"/> <meta name="prism.rightsAgent" content="journalpermissions@springernature.com"/> <meta name="prism.url" content="https://link.springer.com/article/10.1007/s00109-016-1500-6"/> <meta name="prism.doi" content="doi:10.1007/s00109-016-1500-6"/> <meta name="citation_pdf_url" content="https://link.springer.com/content/pdf/10.1007/s00109-016-1500-6.pdf"/> <meta name="citation_fulltext_html_url" content="https://link.springer.com/article/10.1007/s00109-016-1500-6"/> <meta name="citation_journal_title" content="Journal of Molecular Medicine"/> <meta name="citation_journal_abbrev" content="J Mol Med"/> <meta name="citation_publisher" content="Springer Berlin Heidelberg"/> <meta name="citation_issn" content="1432-1440"/> <meta name="citation_title" content="Epithelial-mesenchymal plasticity in circulating tumor cells"/> <meta name="citation_volume" content="95"/> <meta name="citation_issue" content="2"/> <meta name="citation_publication_date" content="2017/02"/> <meta name="citation_online_date" content="2016/12/24"/> <meta name="citation_firstpage" content="133"/> <meta name="citation_lastpage" content="142"/> <meta name="citation_article_type" content="Review"/> <meta name="citation_language" content="en"/> <meta name="dc.identifier" content="doi:10.1007/s00109-016-1500-6"/> <meta name="DOI" content="10.1007/s00109-016-1500-6"/> <meta name="size" content="249049"/> <meta name="citation_doi" content="10.1007/s00109-016-1500-6"/> <meta name="citation_springer_api_url" content="http://api.springer.com/xmldata/jats?q=doi:10.1007/s00109-016-1500-6&api_key="/> <meta name="description" content="Epithelial-to-Mesenchymal Transition (EMT) is a complex process that supports the migratory capacity of epithelial tumor cells and is thought to play a cru"/> <meta name="dc.creator" content="Alix-Panabières, Catherine"/> <meta name="dc.creator" content="Mader, Sonja"/> <meta name="dc.creator" content="Pantel, Klaus"/> <meta name="dc.subject" content="Molecular Medicine"/> <meta name="dc.subject" content="Human Genetics"/> <meta name="dc.subject" content="Internal Medicine"/> <meta name="citation_reference" content="citation_journal_title=Cell; 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Despite the wealth of experimental data, the exact role of EMT in cancer patients remains more controversial. Over the past 10 years, sensitive technologies that allow the detection and molecular characterization of circulating tumor cells (CTCs) in the peripheral blood of tumor patients have been developed. These analyses help to shed new light into the importance of EMT for human tumor cell dissemination. CTCs with mesenchymal features can be attributed in some clinical studies (in particularly on breast cancer) to higher disease stages, presence of metastases, and even to therapy response and worse outcome. However, the published studies addressing the impact of mesenchymal-like CTCs show heterogeneity with regard to assay specificity, size of cancer and control groups, and endpoint parameters. In the present review, we present the key features of the biology of CTCs in relation to epithelial-to-mesenchy-mal plasticity, describe the current technologies for enrichment and detection of CTCs with high epithelial-mesenchymal plasticity, and discuss the clinical studies that have assessed the relevance of mesenchymal CTCs in carcinoma patients."/> <meta property="og:image" content="https://static-content.springer.com/image/art%3A10.1007%2Fs00109-016-1500-6/MediaObjects/109_2016_1500_Fig1_HTML.gif"/> <meta name="format-detection" content="telephone=no"> <link rel="apple-touch-icon" sizes="180x180" href=/oscar-static/img/favicons/darwin/apple-touch-icon-92e819bf8a.png> <link rel="icon" type="image/png" sizes="192x192" href=/oscar-static/img/favicons/darwin/android-chrome-192x192-6f081ca7e5.png> <link rel="icon" type="image/png" sizes="32x32" href=/oscar-static/img/favicons/darwin/favicon-32x32-1435da3e82.png> <link rel="icon" type="image/png" sizes="16x16" 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Despite the wealth of experimental data, the exact role of EMT in cancer patients remains more controversial. Over the past 10 years, sensitive technologies that allow the detection and molecular characterization of circulating tumor cells (CTCs) in the peripheral blood of tumor patients have been developed. These analyses help to shed new light into the importance of EMT for human tumor cell dissemination. CTCs with mesenchymal features can be attributed in some clinical studies (in particularly on breast cancer) to higher disease stages, presence of metastases, and even to therapy response and worse outcome. However, the published studies addressing the impact of mesenchymal-like CTCs show heterogeneity with regard to assay specificity, size of cancer and control groups, and endpoint parameters. In the present review, we present the key features of the biology of CTCs in relation to epithelial-to-mesenchy-mal plasticity, describe the current technologies for enrichment and detection of CTCs with high epithelial-mesenchymal plasticity, and discuss the clinical studies that have assessed the relevance of mesenchymal CTCs in carcinoma patients.","datePublished":"2016-12-24T00:00:00Z","dateModified":"2016-12-24T00:00:00Z","pageStart":"133","pageEnd":"142","sameAs":"https://doi.org/10.1007/s00109-016-1500-6","keywords":["Circulating tumor cells","Epithelial-to-mesenchymal transition","Tumor cell plasticity","Cancer progression","Tumor dissemination","Molecular Medicine","Human Genetics","Internal Medicine"],"image":["https://media.springernature.com/lw1200/springer-static/image/art%3A10.1007%2Fs00109-016-1500-6/MediaObjects/109_2016_1500_Fig1_HTML.gif"],"isPartOf":{"name":"Journal of Molecular 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class="app-article-masthead__journal-title">Journal of Molecular Medicine</span> </a> <a href="https://link.springer.com/journal/109/aims-and-scope" class="app-article-masthead__submission-link" data-track="click_aims_and_scope" data-track-action="aims and scope" data-track-context="article page" data-track-label="link"> Aims and scope <svg width="16" height="16" focusable="false" role="img" aria-hidden="true" class="u-icon"><use xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#icon-eds-i-arrow-right-medium"></use></svg> </a> <a href="https://www.editorialmanager.com/jmme" class="app-article-masthead__submission-link" data-track="click_submit_manuscript" data-track-context="article masthead on springerlink article page" data-track-action="submit manuscript" data-track-label="link"> Submit manuscript <svg width="16" height="16" focusable="false" role="img" aria-hidden="true" class="u-icon"><use xmlns:xlink="http://www.w3.org/1999/xlink" 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xlink:href="#icon-eds-i-mail-medium"></use></svg></a><sup class="u-js-hide"><a href="#Aff1">1</a>,<a href="#Aff2">2</a></sup>, </li><li class="c-article-author-list__item"><a data-test="author-name" data-track="click" data-track-action="open author" data-track-label="link" href="#auth-Sonja-Mader-Aff3" data-author-popup="auth-Sonja-Mader-Aff3" data-author-search="Mader, Sonja">Sonja Mader</a><sup class="u-js-hide"><a href="#Aff3">3</a></sup> & </li><li class="c-article-author-list__item"><a data-test="author-name" data-track="click" data-track-action="open author" data-track-label="link" href="#auth-Klaus-Pantel-Aff3" data-author-popup="auth-Klaus-Pantel-Aff3" data-author-search="Pantel, Klaus" data-corresp-id="c2">Klaus Pantel<svg width="16" height="16" focusable="false" role="img" aria-hidden="true" class="u-icon"><use xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#icon-eds-i-mail-medium"></use></svg></a><sup class="u-js-hide"><a href="#Aff3">3</a></sup> </li></ul> <div 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rel="nofollow">Explore all metrics <svg class="u-icon app-article-metrics-bar__arrow-icon" width="24" height="24" aria-hidden="true" focusable="false"> <use xlink:href="#icon-eds-i-arrow-right-medium"></use> </svg></a></p> </li> </ul> </div> <div class="u-mt-32"> </div> </header> </div> <div data-article-body="true" data-track-component="article body" class="c-article-body"> <section aria-labelledby="Abs1" data-title="Abstract" lang="en"><div class="c-article-section" id="Abs1-section"><h2 class="c-article-section__title js-section-title js-c-reading-companion-sections-item" id="Abs1">Abstract</h2><div class="c-article-section__content" id="Abs1-content"><p>Epithelial-to-Mesenchymal Transition (EMT) is a complex process that supports the migratory capacity of epithelial tumor cells and is thought to play a crucial role in promoting cancer metastasis. Despite the wealth of experimental data, the exact role of EMT in cancer patients remains more controversial. Over the past 10 years, sensitive technologies that allow the detection and molecular characterization of circulating tumor cells (CTCs) in the peripheral blood of tumor patients have been developed. These analyses help to shed new light into the importance of EMT for human tumor cell dissemination. CTCs with mesenchymal features can be attributed in some clinical studies (in particularly on breast cancer) to higher disease stages, presence of metastases, and even to therapy response and worse outcome. However, the published studies addressing the impact of mesenchymal-like CTCs show heterogeneity with regard to assay specificity, size of cancer and control groups, and endpoint parameters. In the present review, we present the key features of the biology of CTCs in relation to epithelial-to-mesenchy-mal plasticity, describe the current technologies for enrichment and detection of CTCs with high epithelial-mesenchymal plasticity, and discuss the clinical studies that have assessed the relevance of mesenchymal CTCs in carcinoma patients.</p></div></div></section> <div class="c-notes"> <p class="c-notes__text c-status-message--info"> <svg width="24" height="24" focusable="false" role="img" aria-hidden="true" class="c-status-message__icon"> <use xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#icon-eds-i-info-filled-medium"></use> </svg> This is a preview of subscription content, <a id="test-login-banner-link" href="//wayf.springernature.com?redirect_uri=https%3A%2F%2Flink.springer.com%2Farticle%2F10.1007%2Fs00109-016-1500-6%3Ferror%3Dcookies_not_supported%26code%3D22cfcb34-1f11-4b96-9df0-6578f71456fc" data-track="click" data-track-action="login" 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This work was further supported by the FEDER plus the Region Languedoc-Roussillon (GEPETOS project) and the National Institute of Cancer (INCA; to C. Alix-Panabières), and the European Research Council Advanced Investigator grant no. 269081 DISSECT (to K. Pantel).</p></div></div></section><section aria-labelledby="author-information" data-title="Author information"><div class="c-article-section" id="author-information-section"><h2 class="c-article-section__title js-section-title js-c-reading-companion-sections-item" id="author-information">Author information</h2><div class="c-article-section__content" id="author-information-content"><h3 class="c-article__sub-heading" id="affiliations">Authors and Affiliations</h3><ol class="c-article-author-affiliation__list"><li id="Aff1"><p class="c-article-author-affiliation__address">Laboratory of Rare Human Circulating Cells (LCCRH), Department of Cellular and Tissular Biopathology of Tumors, University Medical Centre, 641, avenue du Doyen Gaston Giraud, 34093, Montpellier Cedex 5, France</p><p class="c-article-author-affiliation__authors-list">Catherine Alix-Panabières</p></li><li id="Aff2"><p class="c-article-author-affiliation__address">EA2415 – Help for Personalized Decision: Methodological Aspects, University Institute of Clinical Research (IURC), Montpellier University, Montpellier, France</p><p class="c-article-author-affiliation__authors-list">Catherine Alix-Panabières</p></li><li id="Aff3"><p class="c-article-author-affiliation__address">Department of Tumor Biology, Center of Experimental Medicine, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany</p><p class="c-article-author-affiliation__authors-list">Sonja Mader & Klaus Pantel</p></li></ol><div class="u-js-hide u-hide-print" data-test="author-info"><span class="c-article__sub-heading">Authors</span><ol class="c-article-authors-search u-list-reset"><li id="auth-Catherine-Alix_Panabi_res-Aff1-Aff2"><span class="c-article-authors-search__title u-h3 js-search-name">Catherine Alix-Panabières</span><div class="c-article-authors-search__list"><div class="c-article-authors-search__item c-article-authors-search__list-item--left"><a href="/search?dc.creator=Catherine%20Alix-Panabi%C3%A8res" class="c-article-button" data-track="click" data-track-action="author link - 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id="citeas">Cite this article</h3><p class="c-bibliographic-information__citation">Alix-Panabières, C., Mader, S. & Pantel, K. Epithelial-mesenchymal plasticity in circulating tumor cells. <i>J Mol Med</i> <b>95</b>, 133–142 (2017). https://doi.org/10.1007/s00109-016-1500-6</p><p class="c-bibliographic-information__download-citation u-hide-print"><a data-test="citation-link" data-track="click" data-track-action="download article citation" data-track-label="link" data-track-external="" rel="nofollow" href="https://citation-needed.springer.com/v2/references/10.1007/s00109-016-1500-6?format=refman&flavour=citation">Download citation<svg width="16" height="16" focusable="false" role="img" aria-hidden="true" class="u-icon"><use xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#icon-eds-i-download-medium"></use></svg></a></p><ul class="c-bibliographic-information__list" data-test="publication-history"><li class="c-bibliographic-information__list-item"><p>Received<span class="u-hide">: </span><span class="c-bibliographic-information__value"><time datetime="2016-10-06">06 October 2016</time></span></p></li><li class="c-bibliographic-information__list-item"><p>Revised<span class="u-hide">: </span><span class="c-bibliographic-information__value"><time datetime="2016-11-06">06 November 2016</time></span></p></li><li class="c-bibliographic-information__list-item"><p>Accepted<span class="u-hide">: </span><span class="c-bibliographic-information__value"><time datetime="2016-12-08">08 December 2016</time></span></p></li><li class="c-bibliographic-information__list-item"><p>Published<span class="u-hide">: </span><span class="c-bibliographic-information__value"><time datetime="2016-12-24">24 December 2016</time></span></p></li><li class="c-bibliographic-information__list-item"><p>Issue Date<span class="u-hide">: </span><span class="c-bibliographic-information__value"><time datetime="2017-02">February 2017</time></span></p></li><li class="c-bibliographic-information__list-item c-bibliographic-information__list-item--full-width"><p><abbr title="Digital Object Identifier">DOI</abbr><span class="u-hide">: </span><span class="c-bibliographic-information__value">https://doi.org/10.1007/s00109-016-1500-6</span></p></li></ul><div data-component="share-box"><div class="c-article-share-box u-display-none" hidden=""><h3 class="c-article__sub-heading">Share this article</h3><p class="c-article-share-box__description">Anyone you share the following link with will be able to read this content:</p><button class="js-get-share-url c-article-share-box__button" type="button" id="get-share-url" data-track="click" data-track-label="button" data-track-external="" data-track-action="get shareable link">Get shareable link</button><div class="js-no-share-url-container u-display-none" hidden=""><p class="js-c-article-share-box__no-sharelink-info c-article-share-box__no-sharelink-info">Sorry, a shareable link is not currently available for this article.</p></div><div class="js-share-url-container u-display-none" hidden=""><p class="js-share-url c-article-share-box__only-read-input" 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data-track="click" data-track-action="view keyword" data-track-label="link">Epithelial-to-mesenchymal transition</a></span></li><li class="c-article-subject-list__subject"><span><a href="/search?query=Tumor%20cell%20plasticity&facet-discipline="Biomedicine"" data-track="click" data-track-action="view keyword" data-track-label="link">Tumor cell plasticity</a></span></li><li class="c-article-subject-list__subject"><span><a href="/search?query=Cancer%20progression&facet-discipline="Biomedicine"" data-track="click" data-track-action="view keyword" data-track-label="link">Cancer progression</a></span></li><li class="c-article-subject-list__subject"><span><a href="/search?query=Tumor%20dissemination&facet-discipline="Biomedicine"" data-track="click" data-track-action="view keyword" data-track-label="link">Tumor dissemination</a></span></li></ul><div data-component="article-info-list"></div></div></div></div></div></section> </div> </main> <div class="c-article-sidebar u-text-sm u-hide-print 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