A novel function of junctional adhesion molecule-C in mediating melanoma cell metastasis

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, Samuel T 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.

Original languageEnglish (US)
Pages (from-to)4096-4105
Number of pages10
JournalCancer Research
Volume71
Issue number12
DOIs
StatePublished - Jun 15 2011
Externally publishedYes

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Langer, H. F., Orlova, V. V., Xie, C., Kaul, S., Schneider, D., Lonsdorf, A. S., Fahrleitner, M., Choi, E. Y., Dutoit, V., Pellegrini, M., Grossklaus, S., Nawroth, P. P., Baretton, G., Santoso, S., Hwang, S. T., Arnold, B., & Chavakis, T. (2011). A novel function of junctional adhesion molecule-C in mediating melanoma cell metastasis. Cancer Research, 71(12), 4096-4105. https://doi.org/10.1158/0008-5472.CAN-10-2794