Matriptase-Induced Phosphorylation of MET is Significantly Associated with Poor Prognosis in Invasive Bladder Cancer; an Immunohistochemical Analysis

Hepatocyte growth factor (HGF) plays an important role in cancer progression via phosphorylation of MET (c-met proto-oncogene product, receptor of HGF). HGF-zymogen (pro-HGF) must be processed for activation by HGF activators including matriptase, which is a type II transmembrane serine protease and the most efficient activator. The enzymatic activity is tightly regulated by HGF activator inhibitors (HAIs). Dysregulated pro-HGF activation (with upregulated MET phosphorylation) is reported to promote cancer progression in various cancers. We retrospectively analyzed the expression of matriptase, phosphorylated-MET (phospho-MET) and HAI-1 in tumor specimens obtained from patients with invasive bladder cancer by immunohistochemistry. High expression of phospho-MET and increased expression of matriptase were significantly associated with poor prognosis, and high matriptase/low HAI-1 expression showed poorer prognosis. Furthermore, high expression of matriptase tended to correlate with phosphorylation of MET. Increased expression of matriptase may induce the ligand-dependent activation of MET, which leads to poor prognosis in patients with invasive bladder cancer.