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Interaction of human Thy-1 (CD 90) with the integrin αvβ3 (CD51/CD61): an important mechanism mediating melanoma cell adhesion to activated endothelium

Oncogene volume 24, pages 4710–4720 (2005)Cite this article

Abstract

The expression of the αvβ3 integrin (CD51/CD61) on human melanoma cells has been shown to be associated most closely with tumor progression and metastases formation in melanoma. Here, we demonstrated a specific interaction of the αvβ3 integrin on melanoma cells with the human Thy-1, an inducible cell adhesion molecule expressed on the cell surface of activated endothelial cells (EC). The interaction was shown by the binding of purified Thy-1 protein to αVβ3 transfected cells, to αvβ3-expressing melanoma cells and to purified αVβ3 integrin. Moreover, melanoma cells adhere specifically to Thy-1 transfectants via αvβ3 on melanoma cells showing the functional relevance of this interaction for cell adhesion. Finally, the importance of the αvβ3/Thy-1 interaction for the adhesion of melanoma cells to the activated endothelium was confirmed under static and flow conditions by the inhibition of melanoma cell adhesion to and transmigration across activated EC by blocking the αvβ3/Thy-1 interaction. In conclusion, we have identified a new pair of adhesion molecules Thy-1 and αvβ3 mediating the interaction of melanoma cells and activated EC. These data explain at least in part the high tumorigenicity of αvβ3-expressing melanoma cells and the association of αvβ3-positive melanoma cells with a high risk of metastasis and poor prognosis.

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Acknowledgements

The work was supported by Deutsche Forschungsgemeinschaft (SA-863-02; Bonn, Germany) and the Saxon Academy of Science (Leipzig, Germany). We thank Dr M Averbeck for the help and assistance of the realization of the adhesion assays under flow conditions. We thank Professor M Gawaz (Herzzentrum, Munich, Germany) for providing us the αvβ3-transfected CHO cells. The M21 melanoma cell line and its variant lacking the αv integrin (M21L) were kindly provided by Dr D Cheresh (The Scripps Institute, La Jolla, CA, USA).

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  1. Saxon Academy of Science, D-04107, Leipzig, Germany

    Anja Saalbach, Uwe-Frithjof Haustein & Ulf Anderegg

  2. Department of Dermatology, Venerology and Allergology, University of Leipzig, Stephanstr. 11, D-04103, Leipzig, Germany

    Anne Wetzel, Michael Sticherling & Jan C Simon

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  1. Anja Saalbach
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Correspondence to Anja Saalbach.

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Saalbach, A., Wetzel, A., Haustein, UF. et al. Interaction of human Thy-1 (CD 90) with the integrin αvβ3 (CD51/CD61): an important mechanism mediating melanoma cell adhesion to activated endothelium. Oncogene 24, 4710–4720 (2005). https://doi.org/10.1038/sj.onc.1208559

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