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

Int J Cancer. 2016 Aug 15;139(4):824-35. doi: 10.1002/ijc.30131. Epub 2016 May 5.

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.

Keywords: angiogenesis; antibody; galectin-1; imaging; sprouting; therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibodies, Monoclonal / chemistry
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / pharmacology*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / immunology
  • Antineoplastic Agents / pharmacology*
  • Cell Line
  • Cell Movement / drug effects
  • Cell Survival / drug effects
  • Disease Models, Animal
  • Drug Design*
  • Epitopes / chemistry
  • Epitopes / immunology
  • Female
  • Galectin 1 / antagonists & inhibitors
  • Galectin 1 / chemistry
  • Galectin 1 / genetics
  • Galectin 1 / metabolism*
  • Humans
  • Immunoglobulin G / chemistry
  • Immunoglobulin G / immunology
  • Immunoglobulin G / pharmacology
  • Mice
  • Models, Molecular
  • Molecular Conformation
  • Molecular Imaging
  • Neoplasms / diagnostic imaging
  • Neoplasms / drug therapy
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Neovascularization, Pathologic / genetics
  • Neovascularization, Pathologic / metabolism*
  • Protein Binding
  • Species Specificity
  • Structure-Activity Relationship
  • Xenograft Model Antitumor Assays

Substances

  • Antibodies, Monoclonal
  • Antineoplastic Agents
  • Epitopes
  • Galectin 1
  • Immunoglobulin G