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.
Hiscox
S E
SE
Department of Surgery, University of Wales College of Medicine, Heath Park, Cardiff, U.K.
Hallett
M B
MB
Puntis
M C
MC
Nakamura
T
T
Jiang
W G
WG
D015152:Blotting, Northern; D015153:Blotting, Western; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008024:Ligands; D009367:Neoplasm Staging; D000090063:Proto-Oncogene Mas; D019859:Proto-Oncogene Proteins c-met / Q000096:biosynthesis / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis
D008024:Ligands; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger; D019859:Proto-Oncogene Proteins c-met