Original Paper

Oncogene (2005) 24, 4710–4720. doi:10.1038/sj.onc.1208559 Published online 16 May 2005

Interaction of human Thy-1 (CD 90) with the integrin alphavbold italic beta3 (CD51/CD61): an important mechanism mediating melanoma cell adhesion to activated endothelium

Anja Saalbach1, Anne Wetzel2, Uwe-Frithjof Haustein1, Michael Sticherling2, Jan C Simon2 and Ulf Anderegg1

  1. 1Saxon Academy of Science, D-04107 Leipzig, Germany
  2. 2Department of Dermatology, Venerology and Allergology, University of Leipzig, Stephanstr. 11, D-04103 Leipzig, Germany

Correspondence: A Saalbach, E-mail: saalbach@medizin.uni-leipzig.de

Received 4 October 2004; Revised 6 January 2005; Accepted 26 January 2005; Published online 16 May 2005.

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Abstract

The expression of the alphavbeta3 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 alphavbeta3 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 alphaVbeta3 transfected cells, to alphavbeta3-expressing melanoma cells and to purified alphaVbeta3 integrin. Moreover, melanoma cells adhere specifically to Thy-1 transfectants via alphavbeta3 on melanoma cells showing the functional relevance of this interaction for cell adhesion. Finally, the importance of the alphavbeta3/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 alphavbeta3/Thy-1 interaction. In conclusion, we have identified a new pair of adhesion molecules Thy-1 and alphavbeta3 mediating the interaction of melanoma cells and activated EC. These data explain at least in part the high tumorigenicity of alphavbeta3-expressing melanoma cells and the association of alphavbeta3-positive melanoma cells with a high risk of metastasis and poor prognosis.

Keywords:

Thy-1, alphavbeta3, endothelial cell, adhesion, melanoma

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