Functional expression of HGF and its receptor in human colorectal cancer

Background: Hepatocyte growth factor (HGF) stimulates proliferation, migrat ion and morphogenesis of epithelial cells by specific binding to its recept or c-met. Overexpression of HGF or c-met has been reported for human gastri c or pancreatic cancer. In colorectal cancer overexpression of c-met but no t HGF has been shown. However, elevated HGF serum levels have been detected in colorectal cancer patients. Therefore, the present study was performed to investigate expression patterns of both c-met and HGF in colorectal canc ers and metastasis in comparison to normal mucosa. Furthermore, the mitogen ic actions of HGF on colorectal cancer cells were studied in vitro. Methods : Expression of c-met and HGF were analyzed by RT-PCR and Western blotting anal localized in the tissues utilizing immunohistochemistry. Mitogenic eff ects of HGF were determined in four human colon cancer cell lines by H-3-th ymidine incorporation studies. Results: C-met and HGF mRNA were detectable in 60% of the normal specimen, but in the majority of cancer samples, and i n just 33% of the liver metastasis. In cancer samples a coexpression of c-m et and HGF was detected in 77% of the specimens. The extent of protein expr ession of receptor and ligand correlated with the mRNA expression. Moreover , c-met protein expression was increased 2- to 3-fold in colorectal cancers . C-met was detected in cells of epithelial origin, whereas HGF was express ed by mesenchymal cells. In vitro, HGF significantly stimulated cell growth in all four cell lines. Conclusion: Overexpression of c-met protein in col orectal cancers is combined with an expression of HGF in the majority of ca ses suggesting a paracrine manner of growth enhancement, while only a weak expression of c-met or HGF was detected in metastatic tissues. Copyright (C ) 2000 S. Karger AG, Basel.