β1 integrins play an essential role in adhesion and invasion of pancreatic carcinoma cells
β1 integrins play an essential role in adhesion and invasion of pancreatic carcinoma cells
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DOI：
10.1097/00006676-200003000-00004
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发表时间：
2000-03-01
期刊：
影响因子：
2.9
通讯作者：
Otsuki, M
中科院分区：
文献类型：
--
作者：
Arao, S;Masumoto, A;Otsuki, M
为了探讨β 1整合素在胰腺癌侵袭中的作用，我们分析了β 1整合素活性与人胰腺癌细胞系侵袭能力的关系。流式细胞术检测，AsPC1、BxPC3、PANC1、SU8686、KP1NL、KP2和H48N细胞β 1和α 6亚基高表达，α 2、α 3和α 5表达水平不同。细胞粘附实验显示，α 2 β 1、α 5 β 1和α 6 β 1整合素分别是胶原蛋白、纤维连接蛋白和层粘连蛋白的主要粘附受体。β 1整合素在不同细胞类型上表现出广泛的组成活性。抗β 1单克隆抗体（MAB） TS2/16可以快速激活β 1整合素，因此细胞粘附所需的TS2/16代表了β 1整合素的组成活性水平。值得注意的是，作为体外化学侵袭试验的结果，β 1整合素的组成活性水平与胰腺癌细胞的侵袭能力相关。抑制性抗- 1 MAB 13完全阻断了这些细胞系的侵袭。或者，刺激性抗- β 1 MAB TS2/16强烈抑制侵袭。这些结果表明β 1整合素在胰腺癌细胞侵袭中的重要作用，也提示了细胞侵袭的微妙调节机制。
To investigate the role of beta 1 integrins in pancreatic carcinoma invasion, we analyzed the relationship between the activity of beta 1 integrins and the invasive ability of human pancreatic carcinoma cell lines. AsPC1, BxPC3, PANC1, SU8686, KP1NL, KP2, and H48N cells had high expression of beta 1 and alpha 6 subunits, and various levels of alpha 2, alpha 3, and alpha 5 expression as determined by flow cytometry. Cell adhesion assay revealed that alpha 2 beta 1, alpha 5 beta 1, and alpha 6 beta 1 integrins were the predominant adhesion receptors for collagen, fibronectin, and laminin, respectively. beta 1 integrins on different cell types showed a wide range of constitutive activity. Anti-beta 1 monoclonal antibody (MAB) TS2/16 rapidly activated beta 1 integrins, and thus TS2/16 requirement in cell adhesion represented the levels of constitutive activity of beta 1 integrins. Notably, as the result of in vitro chemoinvasion assay, the levels of constitutive activity of beta 1 integrins correlated with the invasive ability of pancreatic carcinoma cells. The inhibitory anti-beta 1 MAB 13 completely blocked the invasion of these cell lines. Alternatively, the stimulatory anti-beta 1 MAB TS2/16 strongly inhibited the invasion. These results show an essential role of beta 1 integrins in invasion of pancreatic carcinoma cells and also suggest subtle regulatory mechanisms of cell invasion.