title: Melanoma cells use Thy-1 (CD90) on endothelial cells for metastasis formation.
abstract: The cell adhesion molecule Thy-1 (CD90) mediates the adhesion of melanoma cells to activated human endothelial cells (EC) via the interaction with the αvβ3-integrin on the tumor cells in vitro. Here, we report a strong expression of Thy-1 on both blood vessel and lymphatic EC in melanoma and melanoma metastases. Vascular endothelial growth factor and tumor necrosis factor-α were identified as inducers of Thy-1 expression on EC in vitro. The physiological role of Thy-1 for lymphogenic and hematogenic metastasis of melanoma cells was substantiated in an experimental metastasis model using B16/F10 melanoma cells. Mice lacking Thy-1 showed markedly diminished experimental lung metastasis after injection of B16/F10 melanoma cells compared to wild-type littermate controls. In addition, on generation of a primary subcutaneous tumor, metastasis to regional lymph nodes was clearly reduced in Thy-1(-/-) mice. However, Thy-1 deletion did not affect subcutaneous primary tumor growth, tumor-induced recruitment of inflammatory cells or T cells, angiogenesis, or T-cell activation. In conclusion, Thy-1 contributes to metastasis of melanoma cells by mechanisms likely involving a Thy-1-mediated adhesion of melanoma cells to EC.
authors.affiliation: Department of Dermatology, Venerology and Allergology, Medical Faculty of the Leipzig University, Leipzig, Germany.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Schubert
authors.forename: Danny
authors.initials: D
authors.lastname: Gutknecht
authors.forename: Margarethe
authors.initials: M
authors.lastname: Köberle
authors.forename: Ulf
authors.initials: U
authors.lastname: Anderegg
authors.forename: Anja
authors.initials: A
authors.lastname: Saalbach
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D042783:Endothelial Cells / Q000378:metabolism; D004729:Endothelium, Lymphatic / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000556:secondary; D008207:Lymphatic Metastasis; D008545:Melanoma / Q000378:metabolism / Q000473:pathology / Q000556:secondary*; D008546:Melanoma, Experimental / Q000378:metabolism / Q000473:pathology / Q000556:secondary; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009368:Neoplasm Transplantation; D012878:Skin Neoplasms / Q000378:metabolism / Q000556:secondary; D018800:Thy-1 Antigens / Q000502:physiology*; D014183:Transplantation, Heterologous; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology
chemical_list: D018800:Thy-1 Antigens; D014409:Tumor Necrosis Factor-alpha; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A