Molecular and Cellular Pathobiology A Novel Function of Junctional Adhesion Molecule-C in Mediating Melanoma Cell Metastasis

نویسندگان

  • 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
چکیده

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 lungmetastasis. Together, JAM-C represents a novel therapeutic target for melanoma metastasis. Cancer Res; 71(12); 4096–105. 2011 AACR.

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تاریخ انتشار 2011