Altered expression and function of beta1 integrins in a highly metastatic human lung adenocarcinoma cell line.
In order to investigate the relationship between beta1 integrins and the metastatic ability of cancer cells, we established a novel and highly metastatic cell line designated PC9-f9 from a poorly metastatic human lung adenocarcinoma cell line (PC9) in nude mice. PC9-f9 cells showed higher invasive activity in the Matrigel invasion assay than PC9 cells. Additionally, in cell adhesion assays, PC9-f9 cells adhered to laminin more strongly than PC9 cells and, unlike PC9 cells, adhered to collagen type IV and fibronectin. FACS analysis showed expression of the integrins alpha2beta1, alpha3beta1 and alpha6beta1 on both of the cell lines but alpha4beta1 and alpha5beta1 were neo-expressed on PC9-f9 cells. In cell adhesion inhibition assays, alpha3beta1 was the major laminin receptor for PC9 cells but not for PC9-f9 cells. Alternatively, PC9-f9 cells adhered to collagen type IV via alpha2beta1 and adhered to fibronectin mainly via alpha5beta1 but also moderately via alpha4beta1. The pretreatment of PC9-f9 cells with anti-beta1 monoclonal antibodies suppressed lung metastases by more than 50%. These data suggest that the altered expression and function of beta1 integrins allow PC9-f9 cells to become more adhesive and invasive, and lead to increased metastatic potential.
Takenaka
K
K
Fourth Department of Internal Medicine, Nippon Medical School, Bunkyo-ku, Tokyo 113-8602, Japan.
Shibuya
M
M
Takeda
Y
Y
Hibino
S
S
Gemma
A
A
Ono
Y
Y
Kudoh
S
S
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D003094:Collagen / Q000378:metabolism; D004338:Drug Combinations; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D039201:Integrin alpha3beta1; D039041:Integrin alpha4beta1; D039121:Integrin alpha6beta1; D019012:Integrin beta1 / Q000235:genetics / Q000502:physiology*; D016023:Integrins / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology; D007797:Laminin; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis / Q000235:genetics / Q000503:physiopathology*; D009363:Neoplasm Proteins / Q000235:genetics / Q000502:physiology*; D009368:Neoplasm Transplantation; D011509:Proteoglycans; D038981:Receptors, Collagen; D017469:Receptors, Fibronectin / Q000378:metabolism; D016201:Receptors, Lymphocyte Homing / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000378:metabolism / Q000473:pathology
D004338:Drug Combinations; D005353:Fibronectins; D039201:Integrin alpha3beta1; D039041:Integrin alpha4beta1; D039121:Integrin alpha6beta1; D019012:Integrin beta1; D016023:Integrins; D007797:Laminin; D009363:Neoplasm Proteins; D011509:Proteoglycans; D038981:Receptors, Collagen; D017469:Receptors, Fibronectin; D016201:Receptors, Lymphocyte Homing; C059485:matrigel; D003094:Collagen