Department of Cell Biology, Harvard Medical School, Boston, 02115 MA, USA.
Cancer Discov. 2011 Jul;1(2):144-57. doi: 10.1158/2159-8274.CD-11-0010.
Dissemination of ovarian tumors involves the implantation of cancer spheroids into the mesothelial monolayer on the walls of peritoneal and pleural cavity organs. Biopsies of tumors attached to peritoneal organs show that mesothelial cells are not present under tumor masses. We have developed a live, image-based in vitro model in which interactions between tumor spheroids and mesothelial cells can be monitored in real time to provide spatial and temporal understanding of mesothelial clearance. Here we provide evidence that ovarian cancer spheroids utilize integrin- and talin- dependent activation of myosin and traction force to promote mesothelial cells displacement from underneath a tumor cell spheroid. These results suggest that ovarian tumor cell clusters gain access to the sub-mesothelial environment by exerting force on the mesothelial cells lining target organs, driving migration and clearance of the mesothelial cells.
卵巢肿瘤的播散涉及将癌细胞球体植入腹膜和胸腔器官壁的间皮单层中。附着于腹膜器官的肿瘤活检显示，肿瘤块下不存在间皮细胞。我们开发了一种基于活细胞的体外模型，可实时监测肿瘤球体与间皮细胞之间的相互作用，从而提供对间皮清除的空间和时间理解。在这里，我们提供的证据表明，卵巢癌细胞球体利用整合素和塔林依赖性肌球蛋白的激活和牵引力来推动间皮细胞从肿瘤细胞球体下方移位。这些结果表明，卵巢肿瘤细胞簇通过对靶器官衬里的间皮细胞施加力来获得进入亚间皮环境的途径，从而驱动间皮细胞的迁移和清除。
