First Author | Schubert K | Year | 2013 |
Journal | Am J Pathol | Volume | 182 |
Issue | 1 | Pages | 266-76 |
PubMed ID | 23159525 | Mgi Jnum | J:192343 |
Mgi Id | MGI:5464950 | Doi | 10.1016/j.ajpath.2012.10.003 |
Citation | Schubert K, et al. (2013) Melanoma cells use Thy-1 (CD90) on endothelial cells for metastasis formation. Am J Pathol 182(1):266-76 |
abstractText | The cell adhesion molecule Thy-1 (CD90) mediates the adhesion of melanoma cells to activated human endothelial cells (EC) via the interaction with the alphavbeta3-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-alpha 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. |