Geng L, Ali S A, Marshall J F, Mackay C L, Hart I R, Delcommence M, Streuli C H, Rees R C
Department of Life Sciences, Nottingham Trent University, UK.
Clin Exp Metastasis. 1998 Nov;16(8):683-91. doi: 10.1023/a:1006572526520.
CT 26 murine colon carcinoma cells demonstrated directional migration (chemotaxis) in response to fibronectin (FN). Sub-lines were derived by positive and negative selection to FN across Transwell filters of 8 microm pore size. The FL6 sub-line (positively selected) demonstrated a significantly increased chemotactic response (P<0.01) to FN compared with parental CT 26 cells, while the FU7 sub-line (negatively selected) showed a reduced chemotactic response to FN (P<0.01). Comparable levels of alpha4, alpha5, alphav and beta1 integrins, which mediate FN attachment, were expressed on positively and negatively selected sub-lines and parental CT 26 cells. Activation of integrins with Mn2+ suggested that the integrins expressed on FL6 cells were in the fully activated state; in contrast FU7 cells displayed only partially activated integrins. Cell attachment and integrin activation status of the sub-lines correlated with their chemotactic response to FN. In vivo FL6 cells showed a significantly reduced tumour growth rate s.c. and a reduction in the number of lung colonies formed following i.v. injection compared with parental CT 26 and FU7 cells. In contrast FU7 cells displayed a significant increase in s.c. tumour growth and the number of lung colonies when compared with the parental line and FL6 sub-line. The results indicate that interaction between integrin receptors expressed on cancer cells and FN plays a central role in the chemotactic response of CT 26 colon carcinoma cells, and that in this model cells selected for chemotaxis to FN displayed a reduced malignant potential.
CT 26小鼠结肠癌细胞对纤连蛋白（FN）表现出定向迁移（趋化性）。通过在孔径为8微米的Transwell滤器上对FN进行正选和负选获得亚系。与亲代CT 26细胞相比，FL6亚系（正选）对FN的趋化反应显著增强（P<0.01），而FU7亚系（负选）对FN的趋化反应减弱（P<0.01）。介导FN附着的α4、α5、αv和β1整合素在正选和负选亚系以及亲代CT 26细胞上的表达水平相当。用Mn2+激活整合素表明，FL6细胞上表达的整合素处于完全激活状态；相比之下，FU7细胞仅显示部分激活的整合素。亚系的细胞附着和整合素激活状态与其对FN的趋化反应相关。在体内，与亲代CT 26细胞和FU7细胞相比，FL6细胞皮下肿瘤生长速率显著降低，静脉注射后形成的肺集落数量减少。相比之下，与亲代细胞系和FL6亚系相比，FU7细胞皮下肿瘤生长和肺集落数量显著增加。结果表明，癌细胞上表达的整合素受体与FN之间的相互作用在CT 26结肠癌细胞的趋化反应中起核心作用，并且在该模型中，选择对FN趋化的细胞显示出降低的恶性潜能。
