OVEREXPRESSION AND ACTIVATION OF HEPATOCYTE GROWTH-FACTOR SCATTER FACTOR IN HUMAN NON-SMALL-CELL LUNG CARCINOMAS

Hepatocyte growth factor/scatter factor (HGF/SF) stimulates the invasi ve growth of epithelial cells via the c-MET oncogene-encoded receptor. In normal lung, both the receptor and the ligand are detected, and th e latter is known to be a mitogenic and a motogenic factor for both cu ltured bronchial epithelial cells and non-small-cell carcinoma lines. Here, ligand and receptor expression was examined in 42 samples of pri mary human non-small-cell lung carcinoma of different histotype. Each carcinoma sample was compared with adjacent normal lung tissue. The Me t/HGF receptor was found to be 2 to 10-fold increased in 25% of carcin oma samples (P = 0.0113). The ligand, HGF/SF, was found to be 10 to 10 0-fold overexpressed in carcinoma samples (P < 0.0001). Notably, while HGF/SF was occasionally detectable and found exclusively as a single- chain inactive precursor in normal tissues, it was constantly in the b iologically-active heterodimeric form in carcinomas. Immunohistochemic al staining showed homogeneous expression of both the receptor and the ligand in carcinoma samples, whereas staining was barely detectable i n their normal counterparts. These data show that HGF/SF is overexpres sed and consistently activated in non-small-cell lung carcinomas and m ay contribute to the invasive growth of lung cancer.