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.

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

TINARI, Nicola;ROSSI, COSMO;LATTANZIO, ROSSANO;D'EGIDIO, Maurizia;GRASSADONIA, Antonino;NATOLI, Clara;
2014

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.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11564/671948
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