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.

Cancer research (2011-05-20)

Harald F Langer, Valeria V Orlova, Changping Xie, Sunil Kaul, Darius Schneider, Anke S Lonsdorf, Manuela Fahrleitner, Eun Young Choi, Vanessa Dutoit, Manuela Pellegrini, Sylvia Grossklaus, Peter P Nawroth, Gustavo Baretton, Sentot Santoso, Sam T Hwang, Bernd Arnold, Triantafyllos Chavakis

PMID21593193

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.