Inhibition of Tumor Growth and Angiogenesis by SP-2, an Anti–Lectin, Galactoside-Binding Soluble 3 Binding Protein (LGALS3BP) Antibody

Sara Traini,Nicola Tinari,Annalisa Di Risio,Francesca Spinella,Stefano Iacobelli,Clara Natoli,Rossano Lattanzio,Mauro Piantelli,Enza Piccolo,Antonino Grassadonia,Cosmo Rossi,Maurizia D'Egidio,Federica Tomao,Rossana La Sorda,Anna Bagnato

doi:10.1158/1535-7163.mct-12-1117

Abstract

Accumulating evidence indicates that serum and tissue levels of lectin, galactoside-binding soluble 3 binding protein (LGALS3BP), a secreted glycoprotein, are elevated in human cancers. Recently, we have identified LGALS3BP as a factor capable of stimulating angiogenesis of microvascular endothelial cells in vitro as well as in vivo. However, the potential therapeutic implications of LGALS3BP function blockade have not been explored yet. Here, we tested the ability of an anti-LGALS3BP mouse monoclonal antibody, SP-2, to antagonize LGALS3BP-induced angiogenesis and tumor growth. The antibody was found to inhibit endothelial cell tubulogenesis induced by either conditioned medium of breast cancer and melanoma cells or human recombinant LGALS3BP. In addition, SP-2 inhibited phosphorylation of FAK and its recruitment to membrane sites as well as AKT and ERK phosphorylation promoted by LGALS3BP. When used in vivo, the antibody restrained LGALS3BP-stimulated angiogenesis and growth of tumor xenografts. Furthermore, the combination of SP-2 and low-dose bevacizumab was more effective than either agent alone. Taken together, these results lead to consideration of SP-2 as a promising candidate for LGALS3BP-targeted therapy.

Highlights

Lectin, galactoside-binding soluble 3 binding protein (LGALS3BP; known as 90K or Mac-2 BP) is a large glycoprotein that forms oligomers of 1,000 to 1,500 kDa in the extracellular milieu and promotes cell adhesion to matrix proteins [1]
Clinical studies have revealed that high serum or tumor tissue levels of LGALS3BP were associated with a shorter survival in patients with breast carcinoma [3, 4], lymphoma [5], pleural mesothelioma [6], and non–small cell lung carcinoma [7]
SP-2 inhibits tube formation induced by LGALS3BP We previously reported that human recombinant

Summary

Introduction

Galactoside-binding soluble 3 binding protein (LGALS3BP; known as 90K or Mac-2 BP) is a large glycoprotein that forms oligomers of 1,000 to 1,500 kDa in the extracellular milieu and promotes cell adhesion to matrix proteins [1]. Considerable attention has been paid to the potential role of LGALS3BP in the development and progression of human cancer. Clinical studies have revealed that high serum or tumor tissue levels of LGALS3BP were associated with a shorter survival in patients with breast carcinoma [3, 4], lymphoma [5], pleural mesothelioma [6], and non–small cell lung carcinoma [7]. Despite these evidences, little is known regarding the mechanism(s) underlying LGALS3BP activ-. D'Annunzio" University, Chieti; 3Laboratory of Molecular Pathology, Regina Elena National Cancer Institute, Rome; and 4Department of Gynaecology and Obstetrics, Sapienza University of Rome, Rome, Italy

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