Activation of hepatocyte growth factor/scatter factor in colorectal carcinoma.

摘要: Activation of hepatocyte growth factor/scatter factor (HGF/SF) in the extracellular milieu is a critical limiting step HGF/SF-induced signaling pathway mediated by Met receptor tyrosine kinase, which has potentially important roles tumor biology and progression. However, little known concerning regulation HGF/SF activation tumors. Immunoblot analysis revealed that was enhanced significantly colorectal carcinoma tissues compared with corresponding normal mucosa. Serum-free conditioned media cultured human cell lines contained HGF/SF-activating activity, addition single-chain precursor form to serum-free culture these cells resulted HGF/SF-dependent modulation cellular phenotypes, such as increased scattering secretion vascular endothelial factor. This processing activity thrombin treatment but inhibited neutralizing antibody against HGF activator (HGFA), XIIa-like serine proteinase believed be expressed mainly liver. The also recombinant HGFA inhibitor type 1 (HAI-1). presence mRNA protein were confirmed lines. Therefore, extrahepatic expression could responsible for HGF/SF-processing cells. We examined HAI-1 mucosa adenoma-carcinoma sequence. Immunohistochemically, stained weakly enterocytes, immunoreactivity modestly neoplastic differentiation. subcellular localization altered showing basal or cell-stroma interface staining patterns, adenoma supranuclear apical pattern. In contrast HGFA, decreased relative adjacent cells, indicating net balance between shifts favor carcinomas. fact, pro-HGFA active proteins tissue It concluded tumors involved play an role