A novel function of junctional adhesion molecule-C in mediating melanoma cell metastasis |
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| Authors: | Langer Harald F Orlova Valeria V Xie Changping Kaul Sunil Schneider Darius Lonsdorf Anke S Fahrleitner Manuela Choi Eun Young Dutoit Vanessa Pellegrini Manuela Grossklaus Sylvia Nawroth Peter P Baretton Gustavo Santoso Sentot Hwang Sam T Arnold Bernd Chavakis Triantafyllos |
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| Institution: | Experimental Immunology Branch, National Cancer Institute, NIH, Bethesda, Maryland, USA. |
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| Abstract: | 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. |
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