The receptor encoded by the human C‐MET oncogene is expressed in hepatocytes, epithelial cells and solid tumors

Abstract

The human c-MET oncogene encodes a transmembrane tyrosine kinase (p190c-met) with structural and functional features of a growth-factor receptor. Monoclonal antibodies (MAbs) have been used to investigate the distribution of the c-Met protein in human normal and neoplastic tissues. By immunofluorescence microscopy homogeneous expression was detected in normal hepatocytes as well as in epithelial cells lining the stomach, the small and the large intestine. Positive staining was also found in epithelial cells of the endometrium and ovary, and in basal keratinocytes of esophagus and skin. By Northern blot analysis, high levels of c-met messenger RNA were detected in specimens of liver, gastro-intestinal tract and kidney. c-met-specific mRNA was also found in thyroid, pancreas and placenta, in which organs c-Met protein was barely detectable by immunofluorescence. The antibodies revealed expression of c-MET protein in hepatomas (11/14), carcinomas of colon and rectum (19/21), stomach (11/22), kidney (16/19), ovary (9/17) and skin (7/17). Carcinomas of the lung (13/20), thyroid (11/13) and pancreas (5/7) were also positive. In these last cases (lung, thyroid and pancreas) tumor cells were homogeneously stained by the antibodies, whereas in their normal counterparts staining was barely detectable. These data suggest that the receptor encoded by c-MET plays a physiological role in epithelial cell growth and that its expression is altered in human carcinomas.

Overexpression and activation of hepatocyte growth factor/scatter factor in human non-small-cell lung carcinomas

“…It is known that the Met/HGF receptor is expressed in the normal lung, in primary NSCLC and in NSCLC cell lines (Di Renzo et al, 1991;Prat et al, 1991;Tsao et al, 1993;Liu and Tsao, 1993). On the contrary, HGF/SF mRNA was detected only at a very low level by reverse transcriptasepolymerase chain reaction in the normal lung.…”

“…The HGF/SF receptor, encoded by the c-MET oncogene (for a review, see Comoglio, 1993), is expressed in several normal human epithelial tissues and is often overexpressed in carcinomas (Di Renzo et al, 1991, 1992, 1995aPrat et al, 1991).…”

Expression of HGF/SF in mesothelioma cell lines and its effects on cell motility, proliferation and morphology

“…Because of its varied biological properties, the expression of HGF/SF in tumours may well act to enhance cell growth and spread and to stimulate metastasis. An increasing number of reports have recorded that both HGF/SF and its receptor, Met, are expressed, and often overexpressed, in various cancers, such as bladder, lung, pancreas, thyroid, colon and stomach carcinoma (Di Renzo et al, 1991Prat et al, 1991;Natali et al, 1993;Joseph et al, 1995). In breast cancer, the level of HGF/SF associated with tumour material has been reported to be a strong indicator of recurrence and predictor of survival (Yamashita et al, 1994 (Rong et al, 1992).…”

A src-Related Kinase in the Brush Border Membranes of Gastrointestinal Cells Is Regulated by c-met

“…Previous reports of localization of c-met in epithelial cells are inconsistent. Both in polarized MDCK cells and in human intestinal cells, the receptor has been shown to be heavily distributed to basolateral membranes with negligible or low levels detected in the apical domains [10,11,31]. In contrast, the HGF receptor has been detected in the luminal membranes of rodent intestine and a number of carcinomas, including those of the pancreas and biliary tree [12-14, 22, 32-34].…”