Expression of the HGF/SF receptor, c-met, and its ligand in human colorectal cancers.

The c-met proto-oncogene product is a receptor tyrosine kinase that mediates the effects of the multifunctional cytokine hepatocyte growth factor/scatter factor (HGF/SF). We have studied the expression of both the c-met receptor and HGF/SF at both the protein and message level in colorectal cancer tissues of varying disease stage. All of the tumors displayed an overexpression of the c-met mRNA compared to their normal tissue counterparts while 16 of 21 tissues (75%) displayed up-regulation of c-met protein. No HGF/SF mRNA or protein could be detected in either tissue type. Viable tumor cells extracted from cancer tissue exhibited increased motility in response to HGF/SF stimulation demonstrating that c-met was functionally active. No correlation between expression of c-met and tumor stage or degree of differentiation was observed. HGF/SF is known to be a potent stimulator of tumor cell motility and invasion, two cellular properties essential for the metastatic development of cancers. The overexpression of the HGF/SF receptor in colorectal cancers may result in an increased sensitivity to HGF/SF, which may confer an enhanced metastatic potential to the cancer cells within the tumor body.