Prostate stromal cell-derived hepatocyte growth factor induces invasion ofprostate cancer cell line DU145 through tumor-stromal interaction

BACKGROUND. In prostate cancer, several growth factors derived from stromal cells regulate tumor cell growth. Hepatocyte growth factor (HGF) possesses biological activities that promote cancer proliferation and invasion throu gh tumor-stromal interaction. We examined how prostate stromal cell-derived HGF affects invasion of prostate cancer cells through this interaction. METHODS. The effects of HGF, various growth factors (transforming growth fa ctor (TGF)-alpha, TGF-beta 1, basic fibroblast growth factor, keratinocyte growth factor, and platelet-derived growth factor), and conditioned medium (CM) from prostate stromal cells (PrSC) on prostate cancer cells (LNCaP, PC -3, and DU145) were determined by collagen gel invasion assay. DU145 cells and PrSC were cocultured for Matrigel invasion chamber assay. Induction act ivity of CM from cancer cells to stimulate HGF production by PrSC was studi ed by the ELISA method and Western blotting. RESULTS. LNCaP and PC-3 cells did not respond to any of the factors examine d. Invasion of DU145 cells into the collagen gel matrix was induced by HGF and TGF-beta 1, but not by any of the other factors tested. When DU145 cell s were cultured in CM from PrSC or cocultured with PrSC, the cells acquired invasive potential, and this invasion was inhibited by an antibody against HGF, but not against TGF-beta 1. Native-type HGF production in PrSC was en hanced by some unknown inducer(s) produced by cancer cells. CONCLUSIONS. PrSC-derived HGF enhanced invasive activity of the prostate ca ncer cell line DU145 through tumor-stromal interaction, wherein DU145 cells secreted some HGF-inducer(s) for PrSC. (C) 1999 Wiley-Liss, Inc.