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    Circulating tumor cells as a window on metastasis biology in lung cancer.

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    Authors
    Hou, Jian-Mei
    Krebs, Matthew G
    Ward, Timothy H
    Sloane, Robert
    Priest, Lynsey
    Hughes, Andrew
    Clack, Glen
    Ranson, Malcolm R
    Blackhall, Fiona H
    Dive, Caroline
    Affiliation
    Clinical and Experimental Pharmacology Group, University of Manchester, Manchester, United Kingdom.
    Issue Date
    2011-03
    
    Metadata
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    Abstract
    Circulating tumor cell (CTC) number in metastatic cancer patients yields prognostic information consistent with enhanced cell migration and invasion via loss of adhesion, a feature of epithelial-to-mesenchymal transition (EMT). Tumor cells also invade via collective migration with maintained cell-cell contacts and consistent with this is the circulating tumor microemboli (CTM; contiguous groups of tumor cells) that are observed in metastatic cancer patients. Using a blood filtration approach, we examined markers of EMT (cytokeratins, E-cadherin, vimentin, neural cadherin) and prevalence of apoptosis in CTCs and CTM to explore likely mechanism(s) of invasion in lung cancer patients and address the hypothesis that cells within CTM have a survival advantage. Intra-patient and inter-patient heterogeneity was observed for EMT markers in CTCs and CTM. Vimentin was only expressed in some CTCs, but in the majority of cells within CTM; E-cadherin expression was lost, cytoplasmic or nuclear, and rarely expressed at the surface of the cells within CTM. A subpopulation of CTCs was apoptotic, but apoptosis was absent within CTM. This pilot study suggests that EMT is not prosecuted homogeneously in tumor cells within the circulation of lung cancer patients and that collective migration and enhanced survival of cells within CTM might contribute to lung cancer metastasis. Multiplex analysis and further detailed exploration of metastatic potential and EMT in CTCs/CTM is now warranted in a larger patient cohort.
    Citation
    Circulating tumor cells as a window on metastasis biology in lung cancer. 2011, 178 (3):989-96 Am J Pathol
    Journal
    The American Journal of Pathology
    URI
    http://hdl.handle.net/10541/135853
    DOI
    10.1016/j.ajpath.2010.12.003
    PubMed ID
    21356352
    Type
    Article
    Language
    en
    ISSN
    1525-2191
    ae974a485f413a2113503eed53cd6c53
    10.1016/j.ajpath.2010.12.003
    Scopus Count
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    All Christie Publications
    All Paterson Institute for Cancer Research
    Medical Oncology

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