BIOLOGICAL ROLE OF HGF/MET PATHWAY IN RENAL CELL CARCINOMA

Abstract

Purpose Several lines of evidence show that hepatocyte growth factor (HGF) and its receptor MET play a significant role in the progression of various cancers including renal cell carcinoma (RCC). Our objectives were to evaluate the gene expression of HGF and MET in RCC, and to examine the effect of HGF on the biological activities of cultured RCC cells. Materials and Methods We examined the gene expression of HGF and MET in 27 primary RCC tumors by quantitative competitive RT-PCR. The effects of HGF on in vitro chemoinvasion assay and the expression of matrix metalloproteinase-9 (MMP-9), and the induction of Fas-induced apoptosis were studied by transfection of HGF cDNA to cultured RCC cells, Caki-1. Results HGF mRNA and MET mRNA were detected in all surgical specimens. The level of expressed HGF mRNA was proportional with the volume of tumor (r = 0.50, p = 0.015). Caki-1 cells overexpressing HGF cells showed enhanced in vitro invasiveness in the chemoinvasion assay and increased activity of 92 kDa type IV collagenase (MMP-9). The sensitivity to Fas-induced cell death was reduced in HGF transfectants, which was reversed by the presence of anti-HGF antibody. Conclusions HGF enhanced the invasive properties of cultured RCC cells and inhibited Fas-induced apoptosis in vitro. Both HGF and MET mRNA were expressed in RCC tissues tested. Our results indicate that HGF/MET pathway may have a significant role in the progression of RCC.