Hepatocyte growth factor decreases sensitivity to chemotherapeutic agents and stimulates cell adhesion, invasion, and migration.
Hepatocyte growth factor (HGF), also known as scatter factor (SF), plays an important role in cell:cell adhesion, cell proliferation, motility, and invasiveness of epithelial cells and tumor cells. In this study, we examined the effects of HGF on these types of biological activities and chemosensitivity in Chinese hamster ovary (CHO) cells by stable transfection of the HGF gene. HGF-transfected clones produced very high titers of HGF protein, whereas control vector-transfected clones did not produce detectable HGF protein. HGF-transfected clones showed modestly increased proliferation rates and became more resistant to cell death and apoptosis caused by two anticancer drugs, adriamycin (ADR) and camptothecin (CPT), compared to controlvector-transfected clones. Furthermore, HGF-transfected clones also exhibited increased activities of cell adhesion, migration, and invasion. The current study is the first demonstration that overexpression of the HGF gene affects chemosensitivity and cell metastasis behaviors, suggesting that HGF signaling pathway is a promising new target of therapeutic intervention of tumors.
Laboratory of Molecular Oncology, Albert Einstein College of Medicine, New Hyde Park, New York, 11040, USA.
Q
Q
Meng
J M
JM
Mason
D
D
Porti
I D
ID
Goldberg
E M
EM
Rosen
S
S
Fan
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D016466:CHO Cells; D002166:Camptothecin / Q000494:pharmacology; D002448:Cell Adhesion / Q000502:physiology; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D006224:Cricetinae; D004285:Dogs; D004317:Doxorubicin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000502:physiology*; D017228:Hepatocyte Growth Factor / Q000502:physiology*; D014162:Transfection
D000970:Antineoplastic Agents; D017228:Hepatocyte Growth Factor; D004317:Doxorubicin; D002166:Camptothecin