A key role for galectin‐1 in sprouting angiogenesis revealed by novel rationally designed antibodies

Abstract

Galectins are carbohydrate binding proteins that function in many key cellular processes. We have previously demonstrated that galectins are essential for tumor angiogenesis and their expression is associated with disease progression. Targeting galectins is therefore a potential anti-angiogenic and anti-cancer strategy. Here, we used a rational approach to generate antibodies against a specific member of this conserved protein family, i.e. galectin-1. We characterized two novel mouse monoclonal antibodies that specifically react with galectin-1 in human, mouse and chicken. We demonstrate that these antibodies are excellent tools to study galectin-1 expression and function in a broad array of biological systems. In a potential diagnostic application, radiolabeled antibodies showed specific targeting of galectin-1 positive tumors. In a therapeutic setting, the antibodies inhibited sprouting angiogenesis in vitro and in vivo, underscoring the key function of galectin-1 in this process.

Oncogenes overexpressed in metastatic oral cancers from patients with pain: potential pain mediators released in exosomes

“…The top 10 GO processes were enriched for vasculogenesis/angiogenesis (in total, 18 different genes), including circulatory system development (n = 17 genes, FDR = 4.7e−11), blood vessel morphogenesis (n = 13 genes, FDR = 1.72e−10), vascular development (n = 14 genes, FDR = 1.72e−10), angiogenesis (n = 12 genes, FDR = 1.72e−10), tube development (n = 16 genes, FDR = 2.97e−10) and tube morphogenesis (n = 14 genes, FDR = 1.86e−09). Further manual curation using PubMed searches identified 11 additional genes involved in vasculogenesis and/or angiogenesis, including, for example, LAMA4 (increased expression in tumor vessels in renal and colon cancer 16 ), LGALS1 (sprouting angiogenesis 17 ), and F2R (PAR1) and MMP1 (MMP1/PAR1 pro-angiogenic signaling 18 )—total 72.5% (29/40) of genes (Fig. 3 , Supplementary Table S6 ).…”

“…Scientific RepoRtS | (2020) 10:14724 | https://doi.org/10.1038/s41598-020-71298-y www.nature.com/scientificreports/ genes, FDR = 1.72e−10), tube development (n = 16 genes, FDR = 2.97e−10) and tube morphogenesis (n = 14 genes, FDR = 1.86e−09). Further manual curation using PubMed searches identified 11 additional genes involved in vasculogenesis and/or angiogenesis, including, for example, LAMA4 (increased expression in tumor vessels in renal and colon cancer 16 ), LGALS1 (sprouting angiogenesis 17 ), and F2R (PAR1) and MMP1 (MMP1/PAR1 proangiogenic signaling 18 )-total 72.5% (29/40) of genes ( Fig. 3, Supplementary Table S6).…”

Treatment of B-cell precursor acute lymphoblastic leukemia with the Galectin-1 inhibitor PTX008

“…Moreover, PET imaging in mice showed accumulation of two of these derivatives in bone [ 60 ]. In the future, it may be therefore feasible to test out a strategy of combined inhibition of Galectin-1 and Galectin-3 function using small molecule inhibitors or monoclonal antibodies [ 61 – 63 ].…”

Glycobiology Modifications in Intratumoral Hypoxia: The Breathless Side of Glycans Interaction

“…Inhibition of galectin expression, using siRNA or antisense sequences, showed significant results in colon [233], ovarian [234], esophageal [235], hepatocarcinoma [236], glioma [237], glioblastoma [238], and melanoma [239] cell lines. Anti-galectin mAbs and Gal-3 recombinant were also effective in vitro studies with diverse cell lines [240-242]. Other galectin inhibition methods that showed some success including inhibition of biosynthesis of tumor-associated antigens [243], use of modified citrus pectin (MCP) [244], small carbohydrate-based inhibitors, such as ß-galactosides [245], and multivalent and allosteric inhibitors, among others [232].…”