A novel function of junctional adhesion molecule-C in mediating melanoma cell metastasis.
A novel function of junctional adhesion molecule-C in mediating melanoma cell metastasis.
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DOI：
10.1158/0008-5472.can-10-2794
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发表时间：
2011-06-15
期刊：
影响因子：
11.2
通讯作者：
Chavakis T
中科院分区：
文献类型：
--
作者：
Langer HF;Orlova VV;Xie C;Kaul S;Schneider D;Lonsdorf AS;Fahrleitner M;Choi EY;Dutoit V;Pellegrini M;Grossklaus S;Nawroth PP;Baretton G;Santoso S;Hwang ST;Arnold B;Chavakis T
恶性黑色素瘤的血源性播散是一种危及生命的并发症。在这里，我们确定连接黏附分子-C(JAM-C)是黑色素瘤转移到肺部的一个新的参与者。JAM-C在人和小鼠黑色素瘤细胞系、人恶性黑色素瘤以及包括黑色素瘤肺转移在内的转移性黑色素瘤中均有表达。JAM-C在小鼠B16黑色素瘤细胞和内皮细胞上均有表达，促进了黑色素瘤细胞的跨内皮迁移。我们产生了JAM-C失活的小鼠。JAM-C−/−小鼠和内皮特异性JAM-C缺陷小鼠显示显著减少B16黑色素瘤细胞向肺部的转移，而用可溶性JAM-C治疗小鼠可防止黑色素瘤肺转移。总之，JAM-C代表了黑色素瘤转移的一个新的治疗靶点。
Hematogenous dissemination of melanoma is a life-threatening complication of this malignant tumor. Here, we identified Junctional Adhesion Molecule-C (JAM-C) as a novel player in melanoma metastasis to the lung. JAM-C expression was identified in human and murine melanoma cell lines, in human malignant melanoma, as well as in metastatic melanoma including melanoma lung metastasis. JAM-C expressed on both murine B16 melanoma cells as well as on endothelial cells, promoted the transendothelial migration of the melanoma cells. We generated mice with inactivation of JAM-C. JAM-C−/− mice as well as endothelial-specific JAM-C-deficient mice displayed significantly decreased B16 melanoma cell metastasis to the lung, whereas treatment of mice with soluble JAM-C prevented melanoma lung metastasis. Together, JAM-C represents a novel therapeutic target for melanoma metastasis.