Normal and malignant prostate epithelial cells differ in their response tohepatocyte growth factor/scatter factor

Hepatocyte growth factor/scatter factor (HGF/SF) promotes the proliferation , differentiation, motility, and invasion of epithelial cells by binding to its cell. surface receptor, the Met tyrosine kinase. In the prostate, Met is expressed predominantly by prostate epithelial cells (PrEC), whereas HGF /SF is synthesized by prostate stromal cells (PrSC). Met is also expressed in localized and metastatic prostate cancers. Our results show that PrECs i n hi vitro culture maintain expression of Met at a level comparable to DU14 5 cancer cell expression. HGF/SF secreted by PrSC stimulates tyrosine phosp horylation of the Met receptor. In normal PrEC, HGF/SF causes growth inhibi tion, sustained phosphorylation of mitogen-activated protein kinase, and in creased CK18 expression consistent with cell differentiation. in contrast, HGF/SF significantly stimulates the proliferation of DU145 prostate cancer cells. HGF/SF in the conditioned medium of PrSC specifically induces migrat ion of both normal and malignant prostate epithelial cells through MatriGel -coated Transwell filters. HGF/SF depletion reduces cell migration by appro ximately 50%. The response of PrEC is specific for HGF/SF since the other g rowth factors tested do not significantly affect growth or migration of PrE Cs. These results support the in vivo importance of the prostate stroma and specifically of HGF/SF as a unique stromal derived factor in the developme nt and progression of prostate cancer.