Ali S, Kaur J, Patel K D
Departments of Biochemistry and Molecular Biology and Physiology and Biophysics, Immunology Research Group, University of Calgary, Alberta, Canada.
Am J Pathol. 2000 Jul;157(1):313-21. doi: 10.1016/S0002-9440(10)64542-7.
Eosinophils are usually associated with parasitic and allergic diseases; however, eosinophilia is also observed in several types of human tumors, including breast carcinomas. In this study we examined several human breast carcinoma cell lines for adhesion molecule expression and the ability to bind and activate eosinophils. MDA-MB-435S and MDA-MB-468 cells constitutively expressed both intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) and this expression was enhanced by treatment with tumor necrosis factor-alpha (TNF-alpha). BT-20 and SK-BR-3 cells only expressed ICAM-1 or VCAM-1 after stimulation with TNF-alpha. Eosinophils constitutively bound to MDA-MB-435S cells, but not to BT-20 cells. Stimulation with TNF-alpha slightly enhanced eosinophil adhesion to MDA-MB-435S cells and dramatically increased adhesion to BT-20 cells. Greater than 80% of eosinophil adhesion to these cell lines was blocked with an anti-alpha4-integrin monoclonal antibody. Both MDA-MB-435S and BT-20 cells also released eosinophil activator(s). Supernatants from TNF-alpha-treated, but not control-treated, cell lines increased eosinophil adhesion to fibronectin and increased eosinophil transmigration across fibronectin-coated transwell plates. Enzyme-linked immunosorbent assays showed that TNF-alpha-stimulated breast carcinoma cells released the chemokine regulated on activation, T cell expressed and secreted (RANTES). Addition of an anti-RANTES antibody to breast carcinoma cell supernatants partially blocked eosinophil activation suggesting that RANTES in these supernatants was participating in eosinophil activation. These data show that TNF-alpha-stimulated breast carcinoma cells express mediators that can both bind and activate eosinophils, suggesting a mechanism for eosinophil localization to breast carcinoma sites.
嗜酸性粒细胞通常与寄生虫病和过敏性疾病相关；然而，在包括乳腺癌在内的几种人类肿瘤中也观察到嗜酸性粒细胞增多。在本研究中，我们检测了几种人类乳腺癌细胞系的黏附分子表达以及结合和激活嗜酸性粒细胞的能力。MDA-MB-435S和MDA-MB-468细胞组成性表达细胞间黏附分子-1（ICAM-1）和血管细胞黏附分子-1（VCAM-1），用肿瘤坏死因子-α（TNF-α）处理可增强这种表达。BT-20和SK-BR-3细胞仅在TNF-α刺激后表达ICAM-1或VCAM-1。嗜酸性粒细胞组成性地与MDA-MB-435S细胞结合，但不与BT-20细胞结合。TNF-α刺激略微增强了嗜酸性粒细胞对MDA-MB-435S细胞的黏附，并显著增加了对BT-20细胞的黏附。超过80%的嗜酸性粒细胞对这些细胞系的黏附被抗α4整合素单克隆抗体阻断。MDA-MB-435S和BT-20细胞也都释放嗜酸性粒细胞激活剂。来自TNF-α处理而非对照处理的细胞系的上清液增加了嗜酸性粒细胞对纤连蛋白的黏附，并增加了嗜酸性粒细胞穿过纤连蛋白包被的Transwell小室板的迁移。酶联免疫吸附测定表明，TNF-α刺激的乳腺癌细胞释放了趋化因子调节激活正常T细胞表达和分泌因子（RANTES）。向乳腺癌细胞上清液中添加抗RANTES抗体可部分阻断嗜酸性粒细胞的激活，表明这些上清液中的RANTES参与了嗜酸性粒细胞的激活。这些数据表明，TNF-α刺激的乳腺癌细胞表达可结合并激活嗜酸性粒细胞的介质，提示了嗜酸性粒细胞定位于乳腺癌部位的一种机制。
