Altered expression and function of beta 1 integrins in a highly metastatichuman lung adenocarcinoma cell line

In older to investigate the relationship between beta1 integrins and the me tastatic ability of cancer cells, we established a novel and highly metasta tic cell line designated PC9-f9 from a poorly metastatic human lung adenoca rcinoma cell line (PC9) in nude mice. PC9-f9 cells showed higher invasive a ctivity in the Matrigel invasion assay than PCB cells. Additionally, in cel l adhesion assays, PC9-f9 cells adhered to laminin more strongly than PC9 c ells and, unlike PC9 cells, adhered to collagen type IV and fibronectin. FA GS analysis showed expression of the integrins alpha2 beta1, alpha3 beta1 a nd alpha6 beta1 on both of the cell lines but alpha4 beta1 and alpha5 beta1 were neo-expressed on PC9-f9 cells. In cell adhesion inhibition assays, al pha3 beta1 was the major laminin receptor for PC9 cells but not for PC9-f9 cells. Alternatively, PC9-f9 cells adhered to collagen type IV via alpha2 b eta1 and adhered to fibronectin mainly via alpha5 beta1 but also moderately via alpha4 beta1. The pretreatment of PC9-f9 cells with anti-beta1 monoclo nal antibodies suppressed lung metastases by more than 50%. These data sugg est that the altered expression and function of beta1 integrins allow PC9-f 9 cells to become more adhesive and invasive, and lend to increased metasta tic potential.