Yamashita Manabu, Ino Asami, Kawabata Kenji, Sakurai Fuminori, Mizuguchi Hiroyuki
National Institute of Biomedical Innovation, Ibaraki, Osaka 567-0085, Japan.
Int J Cancer. 2007 Oct 15;121(8):1690-6. doi: 10.1002/ijc.22852.
The coxsackie and adenovirus receptor (CAR) is involved in the epithelial cell tight junction, the downregulated expression of which is observed in different cancer types. In the present study, we examined CAR's role in tumor metastasis using a B16 melanoma and CT26 colon adenocarcinoma model of experimental metastasis. In lung metastasis, the colony number of B16 cells stably expressing CAR (B16CAR) was significantly lower than that of the control CAR-negative B16 cells. B16 and CT26 cells transiently expressing CAR, which were transduced with adenovirus (Ad) vector expressing CAR, also reduced lung metastasis, suggesting that CAR plays a role in the early stage of metastasis. CAR expression significantly decreased the accumulation of B16 cells in the lung after i.v. injection and the migration in vitro. CAR expression reduced expression of alpha(v), alpha(4), beta(3) and beta(1) integrin, which play important roles in attachment to cells or basement membrane. Thus, CAR expression likely acts as a metastatic suppressor.
柯萨奇病毒和腺病毒受体（CAR）参与上皮细胞紧密连接，在不同癌症类型中均观察到其表达下调。在本研究中，我们使用B16黑色素瘤和CT26结肠腺癌实验性转移模型研究了CAR在肿瘤转移中的作用。在肺转移中，稳定表达CAR的B16细胞（B16CAR）的集落数显著低于对照CAR阴性的B16细胞。用表达CAR的腺病毒（Ad）载体转导的瞬时表达CAR的B16和CT26细胞也减少了肺转移，这表明CAR在转移的早期阶段起作用。CAR表达显著降低了静脉注射后B16细胞在肺中的积聚以及体外迁移。CAR表达降低了α（v）、α（4）、β（3）和β（1）整合素的表达，这些整合素在细胞与细胞或基底膜的附着中起重要作用。因此，CAR表达可能起到转移抑制作用。
