Regulatory role of tetraspanin CD9 in tumor-endothelial cell interaction during transendothelial invasion of melanoma cells
Regulatory role of tetraspanin CD9 in tumor-endothelial cell interaction during transendothelial invasion of melanoma cells
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DOI：
10.1182/blood.v98.13.3717
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发表时间：
2001-12-15
期刊：
影响因子：
20.3
通讯作者：
Sánchez-Mateos, P
中科院分区：
文献类型：
--
作者：
Longo, N;Yáñez-Mó, M;Sánchez-Mateos, P
肿瘤细胞（TCs）和内皮细胞（ECs）之间的异型相互作用可能在肿瘤细胞的血管播散和肿瘤病理性血管生成过程中起关键作用。为了确定参与这些过程的分子，我们首先利用生长在二维胶原上的TC-EC镶嵌单层，通过免疫荧光研究了血管连接蛋白在异源细胞间接触部位的分布。四跨蛋白超家族的几个成员，包括CD9、CD81和CD151，被发现定位于TC-EC接触区。在tc通过生长在三维胶原基质上的EC单层的主动迁移过程中，也观察到四跨蛋白在TC-EC异种接触区域的定位。延时免疫荧光共聚焦显微镜的动态研究显示内皮细胞CD9主动重新分布到黑色素瘤的插入点。发现抗cd9单克隆抗体特异性抑制黑色素瘤细胞的跨内皮迁移；抑制作用可能是由于cd9介导的tc与EC单层的异型相互作用增强所致。这些数据支持了四联蛋白介导的TC跨细胞迁移的新机制，该机制独立于转移过程中TC的运动和生长，以及这些分子在肿瘤血管生成过程中TC- ec镶嵌单层形成中的作用。(C) 2001年由美国血液学会出版。
Heterotypic interaction among tumor cells (TCs) and endothelial cells (ECs) may play a critical role during the vascular dissemination of neoplastic cells and during pathologic angiogenesis in tumors. To identify molecules involved in these processes, the distribution of vascular junctional proteins was first studied by immunofluorescence at sites of heterologous intercellular contact using TC-EC mosaic monolayers grown on 2-dimensional collagen. Several members of the tetraspanin superfamily, including CD9, CD81, and CD151, were found to localize at the TC-EC contact area. The localization of tetraspanins to the TC-EC heterologous contact area was also observed during the active transmigration of TCs across EC monolayers grown onto 3-dimensional collagen matrices. Dynamic studies by time-lapse immunofluorescence confocal microscopy showed an active redistribution of endothelial CD9 to points of melanoma insertion. Anti-CD9 monoclonal antibodies were found to specifically inhibit the transendothelial migration of melanoma cells; the inhibitory effect was likely caused by a strengthening of CD9-mediated heterotypic interactions of TCs to the EC monolayer. These data support a novel mechanism of tetraspanin-mediated regulation of TC transcellular migration independent of TC motility and growth during metastasis and a role for these molecules in the formation of TC-EC mosaic monolayers during tumor angiogenesis. (C) 2001 by The American Society of Hematology.