Trans-homophilic interaction of CADM1 promotes organ infiltration of T-cell lymphoma by adhesion to vascular endothelium.
Trans-homophilic interaction of CADM1 promotes organ infiltration of T-cell lymphoma by adhesion to vascular endothelium.
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恶性细胞器官浸润的初始步骤是与宿主血管内皮细胞的相互作用，这通常由细胞粘附分子的特定组合介导。细胞粘附分子1（CADM 1）在成人T细胞白血病/淋巴瘤（ATL）中过表达，并提供细胞表面诊断标志物。CADM 1促进ATL细胞与血管内皮细胞的粘附和小鼠多器官浸润。然而，其在宿主细胞上的结合伴侣尚未被鉴定。在这项研究中，我们表明，CADM 1促进跨内皮迁移的ATL细胞除了粘附到血管内皮细胞。此外，CADM 1在尾静脉注射后增强小鼠T细胞淋巴瘤细胞EL 4的肝脏浸润，而缺乏粘附活性的CADM 1突变体则没有。在原代内皮细胞中表达的已知CADM 1结合蛋白中，当接种到涂覆有这些蛋白的玻璃上时，只有CADM 1和CADM 4可以诱导ATL细胞的形态学延伸。此外，CADM 1介导的EL 4细胞的肝脏浸润在常规和血管内皮特异性Cadm 1敲除小鼠中被取消，而在Cadm 4敲除小鼠中没有被取消。这些结果表明，宿主血管内皮细胞上的CADM 1是ATL和表达CADM 1的其他T细胞淋巴瘤的器官浸润所必需的。 T淋巴瘤细胞和宿主血管内皮细胞之间的反式嗜同性相互作用CADM 1是表达CADM 1的淋巴瘤细胞浸润器官所必需的。
The initial step of organ infiltration of malignant cells is the interaction with host vascular endothelial cells, which is often mediated by specific combinations of cell adhesion molecules. Cell adhesion molecule 1 (CADM1) is overexpressed in adult T‐cell leukemia/lymphoma (ATL) and provides a cell‐surface diagnostic marker. CADM1 promotes the adhesion of ATL cells to vascular endothelial cells and multiple organ infiltration in mice. However, its binding partner on host cells has not yet been identified. In this study, we show that CADM1 promotes transendothelial migration of ATL cells in addition to the adhesion to vascular endothelial cells. Moreover, CADM1 enhances liver infiltration of mouse T‐cell lymphoma cells, EL4, after tail vein injection, whereas a CADM1 mutant lacking adhesive activity did not. Among the known CADM1‐binding proteins expressed in primary endothelial cells, only CADM1 and CADM4 could induce morphological extension of ATL cells when plated onto glass coated with these proteins. Furthermore, CADM1‐mediated liver infiltration of EL4 cells was canceled in conventional and vascular endothelium‐specific Cadm1 knockout mice, whereas it was not canceled in Cadm4 knockout mice. These results suggest that CADM1 on host vascular endothelial cells is required for organ infiltration of ATL and other T‐cell lymphomas expressing CADM1. Trans‐homophilic interaction CADM1 between T‐lymphoma cells and host vascular endothelial cells is required for organ infiltration of lymphoma cells expressing CADM1.
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DOI：
10.1002/stem.2339
发表时间：
2016-07
期刊：
Stem cells (Dayton, Ohio)
影响因子：
--
作者：
Prisco AR;Hoffmann BR;Kaczorowski CC;McDermott-Roe C;Stodola TJ;Exner EC;Greene AS
通讯作者：
Greene AS
影响因子：
5.4
作者：
Dewan, M. Zahidunnabi;Takamatsu, Naofumi;Morishita, Kazuhiro
通讯作者：
Morishita, Kazuhiro
影响因子：
5.3
作者：
Yamada, D;Yoshida, M;Murakami, Y
通讯作者：
Murakami, Y
影响因子：
56.9
作者：
Biederer, T;Sara, Y;Südhof, TC
通讯作者：
Südhof, TC
影响因子：
20.3
作者：
Hasstedt, Sandra J.;Bezemer, Irene D.;Bovill, Edwin G.
通讯作者：
Bovill, Edwin G.