OVEREXPRESSION OF THE MET HGF RECEPTOR IN RENAL-CELL CARCINOMAS/

The c-met oncogene encodes the receptor for hepatocyte growth factor/s catter factor (HGF/SF), a multifunctional cytokine able to mediate mor phogenesis as well as mitogenesis, motogenesis and invasiveness of epi thelial cells. HGF/SF has been implicated in branching tubulogenesis o f the developing kidney and in regeneration after renal injury and nep hrectomy. We have examined the expression of the met/HGF receptor in n ormal human kidney and tissues of the genito-urinary tract, and in SO kidney neoplasms of different histotypes, using monoclonal antibodies (MAbs) against the met/HGF receptor and immunohistochemistry. In norma l kidneys, weak staining restricted to the distal tubules was observed . Transitional cell carcinomas were consistently negative, whereas inc reased expression at various levels was found in 87% of renal cell car cinomas with different cytological features and histological patterns. Western blot analysis of samples showed that the met/HGF receptor fou nd in the malignant cells exhibits features of the normal receptor. Th e met/HGF receptor is also overexpressed in a renal cell carcinoma cel l line, whose motility is triggered by HGF/SF. Our data suggest that e xpression of the met/HGF receptor may be involved in the onset and pro gression of renal cell carcinomas. (C) 1996 Wiley-Liss, Inc.