AUTOCRINE STIMULATION OF MOTILITY IN SBC-5 HUMAN LUNG-CARCINOMA CELLS BY A 2-KRINGLE VARIANT OF HGF

Hepatocyte growth factor (HGF), a ligand for the c-met protooncogene product, is a pleiotropic cytokine which elicits mitogenic, motogenic and morphogenic activities. Among various human lung carcinoma cells, we found that SBC-5 small cell lung carcinoma cells simultaneously expressed the c-Met/HGF receptor and a smaller variant-type of HGF composed of N-terminal two-kringle domains, without expressing authentic heterodimeric HGF. The addition of anti-HGF antibodies to cultures of SBC-5 cells specifically inhibited spreading and motility of the cells without affecting growth, and the conditioned medium of SBC-5 cells also induced scattering of other lineage lung carcinoma. Thus, simultaneous expression of the unique smaller variant HGF and its receptor, c-Met, in SBC-5 cells suggests the involvement of a smaller variant HGF in the development or progression of the lung carcinoma cells, through an autocrine mechanism.