Abstract 2684: Inhibition of tumor growth and angiogenesis by SP-2, an anti-LGALS3BP antibody

Abstract

Abstract Background: Accumulating evidence indicates that serum and tissue levels of the lectin galactoside-binding soluble 3 binding protein (LGALS3BP), a secreted glycoprotein, are elevated in human cancer. Recently, we have identified LGALS3BP as a factor capable of stimulating angiogenesis of microvascular endothelial cells in culture as well as in vivo. However, the potential therapeutic implications of LGALS3BP function blockade, has not been explored yet. Methods: Here we tested the ability of an anti-LGALS3BP monoclonal antibody, named SP-2, to antagonize LGALS3BP-induced angiogenesis and tumor growth. Results: SP-2 dose-dependently inhibited HUVEC tubulogenesis induced by either conditioned medium of breast cancer and melanoma cells or purified recombinant LGALS3BP. This was accompanied by inhibition of FAK, Akt and ERKs phosphorylation as well as FAK recruitment to membrane sites and actin remodeling. In vivo, SP-2 inhibited LGALS3BP-stimulated angiogenesis and restrained growth of different xenograft models of human cancer. Finally, the combination of SP-2 with low-dose Bevacizumab was more effective than either agent alone in suppressing angiogenesis and tumor growth. Conclusions: Targeting LGALS3BP with SP-2 could represent a promising therapeutic approach for LGALS3BP expressing tumors. Citation Format: Enza Piccolo, Sara Trani, Nicola Tinari, Cosmo Rossi, Rossana La Sorda, Rossano Lattanzio, Maurizia D'Egidio, Annalisa Di Risio, Antonino Grassadonia, Francesca Spinella, Anna Bagnato, Mauro Piantelli, Clara Natoli, Stefano Iacobelli. Inhibition of tumor growth and angiogenesis by SP-2, an anti-LGALS3BP antibody. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2684. doi:10.1158/1538-7445.AM2014-2684