2011•Cancer ResearchOpen access
A Novel Function of Junctional Adhesion Molecule-C in Mediating Melanoma Cell Metastasis
Harald F. Langer, Valeria V. Orlova, Changping Xie, Sunil C. Kaul, Darius Schneider, Anke S. Lonsdorf, Manuela Fahrleitner, Eun Young Choi, Vanessa Dutoit, Manuela Pellegrini, Sylvia Großklaus, Peter P. Nawroth, Gustavo Baretton, Sentot Santoso, Samuel Hwang, Bernd Arnold, Triantafyllos Chavakis
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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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