Abstract
Autocrine stimulation via coexpression of hepatocyte growth factor (HGF) and its receptor (Met) has been reported in many human sarcomas, but few in carcinomas. In this report, we found that one gastric cancer cell line, SNU-484, among 11 gastric cell lines tested has an autocrine HGF- Met stimulation. RT-PCR, ELISA and scattering assay using MDCK cells revealed that SNU-484 cells secreted a significant amount of active HGF (about 1.25 +/- 0.41 ng/24 h/10(6) cells) into conditioned medium. Resultantly, Met in this cell line was constitutively phosphorylated. Neutralizing antibodies against HGF reduced the tyrosine phosphorylation of Met, resulting in the inhibition of cell proliferation and migration (P <0.005). To the best of our knowledge, this is the first report on autocrine HGF-Met signaling in a gastric cancer cell line. Our observations with SNU-484 cells suggest that HGF is involved in the development and/or progression of some gastric carcinoma through an autocrine mechanism.
Highlights
The proto-oncogene c-met encodes a 190 kDa heterodimeric transmembrane tyrosine kinase which has been identified as the receptor of hepatocyte growth factor (HGF, known as scatter factor) (Bottaro et al, 1991)
Whereas low or undetectable levels of Met mRNA are found in normal mucosa, much higher level of mRNA has been observed in their malignant counterpart (Di Renzo et al, 1991; Kaji et al, 1996), suggesting involvement of HGF signaling in gastric cancer formation and/or progression
These results strongly suggest that the Met overexpression and the paracrine interaction of HGF with Met may play an important role in the tumorigenesis and progression of gastric carcinoma
Summary
The proto-oncogene c-met encodes a 190 kDa heterodimeric transmembrane tyrosine kinase which has been identified as the receptor of hepatocyte growth factor (HGF, known as scatter factor) (Bottaro et al, 1991). It has been reported that HGF level in serum or tumor tissue was highly elevated in gastric cancer patients (Han et al, 1998), and that the increase of serum HGF level was significantly correlated with the progression of tumor stage (Han et al, 1999). Taken together, these results strongly suggest that the Met overexpression and the paracrine interaction of HGF with Met may play an important role in the tumorigenesis and progression of gastric carcinoma. Vol 37(3), 213- 219, 2005 of gastric cancer cells
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