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Versican Accumulation in Human Prostatic Fibroblast Cultures Is Enhanced by Prostate Cancer Cell-derived Transforming Growth Factor ß1¹

Flinders Cancer Centre, Department of Surgery, Flinders University School of Medicine and Flinders Medical Centre, Adelaide, South Australia 5042, Australia [A. J. S., C. R., K. M., W. D. T., D. J. H.], and Division of Life Sciences, Cell and Molecular Biology, University of Texas at San Antonio, San Antonio, Texas 78249 [R. G. L.].

We have previously demonstrated that peritumoral stromal matrix derived from prostate cancer patients who relapse after radical surgery contains elevated levels of versican. The purpose of this study was to determine whether prostate cancer cells control stromal cell secretion of versican. Serum-free conditioned medium from three prostate adenocarcinoma cell lines, LNCaP, PC3, and DU145, was added to cultures of fibroblasts established from prostatic tissue of patients with benign prostatic hyperplasia, and the medium was harvested at 24, 48, and 72 h. Immunoblotting with an antiversican core protein antibody revealed that prostatic fibroblast medium harvested at 72 h contained increased levels of versican after treatment with either LNCaP-, PC3- or DU145-conditioned medium (2.5-, 4.5-, and 5-fold, respectively) compared with control cultures. This increase in versican in the culture medium was not observed after coincubation with transforming growth factor ß1-neutralizing antisera. The results of this study suggest that prostate tumor cells induce host stromal cells to secrete increased versican levels via a paracrine mechanism mediated by transforming growth factor ß1.

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