DIFFERENTIAL EXPRESSION OF MET HEPATOCYTE GROWTH-FACTOR RECEPTOR IN SUBTYPES OF NONSMALL CELL LUNG CANCERS

Hepatocyte growth factor (HGF)/scatter factor (SF) is a multifunctiona l factor that stimulates epithelial cell motility, invasion and morpho genesis, Its receptor is a transmembrane tyrosine kinase encoded by th e Met proto-oncogene. Several studies have suggested a possible role f or HGF/Met in tumor development and progression. To investigate the po tential roles of Met in human lung cancer biology, we have studied the mRNA and protein expression of Met in normal lung tissue, primary non -small cell lung carcinoma (NSCLC), and NSCLC cell lines. The results indicated a differential pattern of Met expression among various subty pes of NSCLC. The majority of squamous cell carcinoma (SQCC), either i n vivo or in vitro, expressed Met mRNA and its protein product at leve ls much lower than or similar to normal lung tissue or bronchial epith elium. Moreover, SQCC characteristically over-expressed a variant Met mRNA which corresponds to a 5' partially deleted transcript produced b y alternative splicing. In contrast, the expression of Met mRNA and it s protein product in adenocarcinoma (ADC) and large cell undifferentia ted carcinoma were more heterogeneous. Overexpression was demonstrated in approximately 35% and 20% of these subtypes of NSCLC, respectively . Among ADC, intermediate to high levels of Met immunoreactivity corre lated with greater degree of tumor differentiation. Furthermore, an ac centuation of Met immunoreactivity was often noted in cancer cells at the advancing edge of tumors. These findings support a role for Met in lung cancer cell invasion and differentiation in vivo, but its expres sion and functions may be modified by the differentiation phenotype of the tumor cells. (C) 1998 Elsevier Science Ireland Ltd. All rights re served.