Autocrine stimulation of motility in SBC-5 human lung carcinoma cells by a two-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.
Itakura
Y
Y
Department of Oncology, Osaka University Medical School, Japan.
Yamamoto
T
T
Matsumoto
K
K
Nakamura
T
T
D002277:Carcinoma / Q000503:physiopathology*; D002465:Cell Movement; D015870:Gene Expression; D017228:Hepatocyte Growth Factor / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D018082:Kringles; D008175:Lung Neoplasms / Q000503:physiopathology*; D019859:Proto-Oncogene Proteins c-met; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases / Q000502:physiology; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D012334:RNA, Neoplasm; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met; D020794:Receptor Protein-Tyrosine Kinases