[Tetraspanins: a new target for antiangiogenic therapy?]

Inhibition of the vascular endothelial growth factor A or inhibition of its receptors are currently used for the treatment of cancer. However, the results are still modest, especially because of the multitude and redundancy of angiogenic factors. It can be hypothesized that therapies targeting directly endothelial cells themselves could be more effective. The tetraspanins are transmembrane molecules, which are devoid of intrinsic enzymatic activity but can associate with each other and with other molecules such as integrins or proteins of the immunoglobulin superfamily to form a network. The tetraspanins are present on the surface of endothelial cells and in vitro, inhibition of these molecules by antibodies or small interfering RNA suggests that tetraspanins play a role in angiogenesis. These preliminary data have been confirmed by the study of cancer xenografts in tetraspanin-deficient mice, which have a significant decrease in tumor size and tumor angiogenesis. In vivo, it has been shown that intravenous administration of a monoclonal antibody (ALB6) directed against CD9 decreases the tumor growth and angiogenesis and that intravitreal injection of a small interfering RNA decreasing CD9 significantly inhibits choroidal neovascularization induced by laser. Finally, anti-angiogenic effects and potent anti-tumor activity are observed by the intraperitoneal administration of GS-168AT2, a peptide derived from CD9-Partner 1, a molecule belonging to the immunoglobulin superfamily, which interacts strongly with the CD9 and CD81. These data suggest that the pharmacological modulation of the tetraspanin web could play a new promising anti-angiogenic strategy.