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    Invasive characteristics of human prostatic epithelial cells: understanding the metastatic process.

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    Authors
    Hart, Claire A
    Brown, Michael D
    Bagley, Steven
    Sharrard, M
    Clarke, Noel W
    Affiliation
    PromPT Genito-Urinary Cancer Research, Cancer Research UK Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Wilmslow Road, Manchester M20 4BX, UK.
    Issue Date
    2005-02-14
    
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    Abstract
    Prostate cancer has a predilection to metastasise to the bone marrow stroma (BMS) by an as yet uncharacterised mechanism. We have defined a series of coculture models of invasion, which simulate the blood/BMS boundary and allow the elucidation of the signalling and mechanics of trans-endothelial migration within the complex bone marrow environment. Confocal microscopy shows that prostate epithelial cells bind specifically to bone marrow endothelial-to-endothelial cell junctions and initiate endothelial cell retraction. Trans-endothelial migration proceeds via an epithelial cell pseudopodial process, with complete epithelial migration occurring after 232+/-43 min. Stromal-derived factor-1 (SDF-1)/CXCR4 signalling induced PC-3 to invade across a basement membrane although the level of invasion was 3.5-fold less than invasion towards BMS (P=0.0007) or bone marrow endothelial cells (P=0.004). Maximal SDF-1 signalling of invasion was completely inhibited by 10 microM of the SDF-1 inhibitor T140. However, 10 microM T140 only reduced invasion towards BMS and bone marrow endothelial cells by 59% (P=0.001) and 29% (P=0.011), respectively. This study highlights the need to examine the potential roles of signalling molecules and/or inhibitors, not just in single-cell models but in coculture models that mimic the complex environment of the bone marrow.
    Citation
    Invasive characteristics of human prostatic epithelial cells: understanding the metastatic process. 2005, 92 (3):503-12 Br. J. Cancer
    Journal
    British Journal of Cancer
    URI
    http://hdl.handle.net/10541/76853
    DOI
    10.1038/sj.bjc.6602325
    PubMed ID
    15668715
    Type
    Article
    Language
    en
    ISSN
    0007-0920
    ae974a485f413a2113503eed53cd6c53
    10.1038/sj.bjc.6602325
    Scopus Count
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    All Christie Publications
    All Paterson Institute for Cancer Research

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