title: Inhibition of tumor growth and angiogenesis by SP-2, an anti-lectin, galactoside-binding soluble 3 binding protein (LGALS3BP) antibody.
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.
authors.affiliation: Authors' Affiliations: MediaPharma s.r.l.; Department of Experimental and Clinical Sciences, "G. D'Annunzio" University, Chieti; Laboratory of Molecular Pathology, Regina Elena National Cancer Institute, Rome; and Department of Gynaecology and Obstetrics, Sapienza University of Rome, Rome, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Traini
authors.forename: Enza
authors.initials: E
authors.lastname: Piccolo
authors.forename: Nicola
authors.initials: N
authors.lastname: Tinari
authors.forename: Cosmo
authors.initials: C
authors.lastname: Rossi
authors.forename: Rossana
authors.initials: R
authors.lastname: La Sorda
authors.forename: Francesca
authors.initials: F
authors.lastname: Spinella
authors.forename: Anna
authors.initials: A
authors.lastname: Bagnato
authors.forename: Rossano
authors.initials: R
authors.lastname: Lattanzio
authors.forename: Maurizia
authors.initials: M
authors.lastname: D'Egidio
authors.forename: Annalisa
authors.initials: A
authors.lastname: Di Risio
authors.forename: Federica
authors.initials: F
authors.lastname: Tomao
authors.forename: Antonino
authors.initials: A
authors.lastname: Grassadonia
authors.forename: Mauro
authors.initials: M
authors.lastname: Piantelli
authors.forename: Clara
authors.initials: C
authors.lastname: Natoli
authors.forename: Stefano
authors.initials: S
authors.lastname: Iacobelli
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D000068258:Bevacizumab; D014408:Biomarkers, Tumor / Q000037:antagonists & inhibitors*; D002352:Carrier Proteins / Q000037:antagonists & inhibitors*; D045744:Cell Line, Tumor; D004357:Drug Synergism; D005260:Female; D006023:Glycoproteins / Q000037:antagonists & inhibitors*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008325:Mammary Neoplasms, Experimental; D051379:Mice; D008819:Mice, Nude; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D023041:Xenograft Model Antitumor Assays; D016326:Extracellular Matrix Proteins
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D000068258:Bevacizumab; D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D006023:Glycoproteins; C081856:LGALS3BP protein, human; D016326:Extracellular Matrix Proteins