Original Article

Subject Category: Cell Biology

Journal of Investigative Dermatology (2007) 127, 1615–1621; doi:10.1038/sj.jid.5700778; published online 22 March 2007

Lubrol-RAFTs in Melanoma Cells: A Molecular Platform for Tumor-Promoting Ephrin-B2–Integrin-bold italic beta1 Interaction

Stefanie Meyer1, Evelyn Orsó2, Gerd Schmitz2, Michael Landthaler1 and Thomas Vogt1

  1. 1Department of Dermatology, University Hospital of Regensburg, Regensburg, Germany
  2. 2Institute of Clinical Chemistry, University Hospital of Regensburg, Regensburg, Germany

Correspondence: Dr Stefanie Meyer, Department of Dermatology, University of Regensburg, D-93042 Regensburg, Germany. E-mail: stefanie.meyer@klinik.uni-regensburg.de

Received 14 June 2006; Revised 10 December 2006; Accepted 2 January 2007; Published online 22 March 2007.

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Abstract

Ephrins control cell motility and matrix adhesion. These functions play a pivotal role in cancer progression, for example, in malignant melanomas. We have previously shown that the ephrin-B2-tumor-promoting action is partly mediated by integrin-beta1 interaction. However, the subcellular prerequisites for molecular interaction like molecular proximity and co-compartmentalization have not been elucidated yet. Specific cholesterol-rich microdomains, termed lipid rafts (RAFTs), are known to be essential for functional ephrin-B2 signalling and integrin-mediated effects. Therefore, we addressed the question whether RAFT co-compartmentalization of both molecules could provide the molecular platform for their tumor-promoting interaction. In this study, we show that overexpressed ephrin-B2 is not only compartmentalized to classical Triton X-100 RAFTs in B16 melanoma cells, but also to the recently defined Lubrol-RAFTs. Interestingly, in the melanoma cells investigated, integrin-beta1 is also preferentially detected in such Lubrol-RAFTs. Accordingly, the presence of ephrin-B2 and integrin-beta1 in RAFTs and their function in cell migration and matrix attachment are highly sensitive to RAFT disruption by cholesterol depletion. Confocal fluorescence microscopy analyses also support the concept of a close molecular proximity and functional interplay of ephrin-B2 and integrin-beta1 in the plasma membrane. We conclude that Lubrol-RAFTs probably represent the platform for tumor-promoting ephrin-B2–integrin-beta1 interaction, which could become an interesting target for future antitumoral therapies.

Abbreviations:

CD, methyl-beta-cyclodextrin; MM, malignant melanoma; RAFTs, lipid rafts

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