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Collagen remodelling by osteoblast and prostate vancer vell interactions in metastatic bone lesions

Sturge, Justin



A major clinical complication in patients with advanced prostate cancer is metastasis to bone where osteoblastic and/or osteoclastic activity results in a highly destructive tissue remodelling process.Recent in vivo studies have identified important functions for the collagen-binding receptor, Endo 180 (CD280, uPARAP, MRC2), in both bone development and tumour progression.Our observation of strong Endo180 expression on invading tumour cells residing in prostatic bone lesions (Kogianni et al., 2009) suggests that it can function as part of the collagen degradome to help facilitate bone destruction during the advanced stages of prostate cancer.To mimick this metastatic microenvironment in vitro we have established co-cultures of human primary bone osteoblasts and prostate cells derived from the different stages of disease progression: benign hyperplasia, low and intermediate risk primary tumours and various metastatic lesions.The temporal changes for Endo180 expression in these co-cultures were coordinated with alterations in mineralisation and alkaline phosphatase activity; and collagen production, binding or uptake.Moreover, the normal 'stromal' expression of Endo 180 in osteoblasts was superseded by 'epithelial' expression, which was dramatically upregulated by direct osteoblast-prostate cell interaction but not osteoblast conditioned medium in the more invasive prostate cells.The bone-derived factors involved in this apparent 'mesenchymal-to-epithelial' switch of Endo180 function are a major focus of our ongoing studies, which are ultimately aimed to pinpoint the role of the collagen degradome in the pathology of metastatic bone lesions; and its potential value as a future therapeutic target in prostate cancer patients with advanced disease.

Start Date May 15, 2009
Publication Date Jun 1, 2009
Series Title BIT‘s 2nd Annual World Cancer Congess 2009
Series Number p256
APA6 Citation Sturge, J. (2009). Collagen remodelling by osteoblast and prostate vancer vell interactions in metastatic bone lesions