Role of Hepatocyte Growth Factor, Met, and E-cadherin in the Progression of Gastric Carcinomas

Abstract

Hepatocyte growth factor (HGF) is a glycoprotein secreted from stromal fibroblasts which bind to the transmembrane Met receptor. This receptor is expressed from a variety of tumors, including gastric carcinomas. To look for a possible paracrine loop between gastric cancer cells and their surrounding fibroblasts in a gastric carcinoma, the effect of HGF on the morphology and expression of the cell- adhesion molecule E-cadherin was examined using fifty resected gastric carcinomas. The expression of Met and E-cadherin in primary gastric carcinoma was examined using immunohistochemical staining. The level of HGF in the tumor extracts was determined by using an Immunis HGF EIA kit (Institute of Immunology). The levels of HGF in the tumor extracts correlated significantly with the progression of the tumor stage (p<0.05). The mean level of HGF was significantly higher in the tumors of an undifferentiated type than in those of a differentiated type (p<0.05). Eighty-two percent (82%) of the tumors showed increased Met expression, but no significant correlation was found between Met expression and tumor progression or differentiation. Twenty-six (52%) tumors revealed a preserved E-cadherin expression similar to that of a normal gastric mucosa. Abnormal E-cadherin expression was found in twenty-four tumors (48%). There was a significant correlation between the degree of E-cadherin expression and the progression and differentiation of the tumor. The level of HGF in a tumor with cytoplasmic E-cadherin expression was significantly higher than that with membranous E-cadherin expression. In conclusion : we can conclude that HGF has the ability to modulate E-cadherin expression and induce intracellular translocation of E-cadherin in gastric carcinomas.