Takenaka K, Shibuya M, Takeda Y, Hibino S, Gemma A, Ono Y, Kudoh S
Fourth Department of Internal Medicine, Nippon Medical School, Bunkyo-ku, Tokyo 113-8602, Japan.
Int J Oncol. 2000 Dec;17(6):1187-94. doi: 10.3892/ijo.17.6.1187.
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.
为了研究β1整合素与癌细胞转移能力之间的关系，我们从裸鼠体内低转移潜能的人肺腺癌细胞系（PC9）中建立了一种新的、高转移潜能的细胞系，命名为PC9-f9。在基质胶侵袭试验中，PC9-f9细胞比PC9细胞表现出更高的侵袭活性。此外，在细胞黏附试验中，PC9-f9细胞比PC9细胞更强烈地黏附于层粘连蛋白，并且与PC9细胞不同的是，PC9-f9细胞还能黏附于IV型胶原和纤连蛋白。流式细胞术分析显示，两种细胞系均表达整合素α2β1、α3β1和α6β1，但α4β1和α5β1在PC9-f9细胞中为新表达。在细胞黏附抑制试验中，α3β1是PC9细胞的主要层粘连蛋白受体，但不是PC9-f9细胞的。另外，PC9-f9细胞通过α2β1黏附于IV型胶原，主要通过α5β1并适度通过α4β1黏附于纤连蛋白。用抗β1单克隆抗体预处理PC9-f9细胞可使肺转移减少50%以上。这些数据表明，β1整合素表达和功能的改变使PC9-f9细胞具有更强的黏附性和侵袭性，并导致转移潜能增加。
