Inhibitory effects of Semaphorin 3F as an alternative candidate to anti-VEGF monoclonal antibody on angiogenesis

In Vitro Cell Dev Biol Anim. 2019 Oct;55(9):756-765. doi: 10.1007/s11626-019-00392-x. Epub 2019 Aug 16.

Abstract

Vascular endothelial growth factor (VEGF) inhibition forms the basis for anti-angiogenic therapies. With the methods based on the monoclonal antibody-mediated typical VEGF blockade, pathological angiogenesis in the tumor microenvironment is inhibited and the limitation of tumor growth is provided; however, the existing tumor tissue cannot be intervened. In this study, the anti-angiogenic effects of Semaphorin (SEMA) 3F, which has frequently been reported to have tumor suppressive properties, on a chick chorioallantoic membrane model as well as in vitro cell-cell interactions were investigated and comparatively assessed using anti-VEGF antibody. Vascular endothelial cells and chick embryos were stimulated with 10-16 ng/mL VEGF165 prior to SEMA 3F administration in order to generate pathological vascularization conditions. Both in vitro and in ovo results revealed that SEMA 3F suppressed VEGF165-induced abnormal vascularization more effectively than anti-VEGF. Moreover, the required dose of SEMA 3F was significantly lower than that of anti-VEGF (103 times less under in ovo conditions). In light of these results, SEMA 3F is recommended as an important therapeutic agent for the prevention of pathological angiogenesis. SEMA 3F may offer an effective and efficient anti-angiogenic intervention that can be administered at a lower dose alternative to typical VEGF blocking agents.

Keywords: Angiogenesis; Anti-VEGF antibody; Chick chorioallantoic membrane; Semaphorin 3F; VEGF.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacology
  • Chick Embryo
  • Chorioallantoic Membrane / drug effects
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism
  • Endothelial Cells / pathology
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Membrane Proteins / genetics*
  • Membrane Proteins / pharmacology
  • Morphogenesis / drug effects
  • Neoplasms / drug therapy*
  • Neoplasms / genetics
  • Neoplasms / immunology
  • Neoplasms / pathology
  • Neovascularization, Pathologic / drug therapy*
  • Neovascularization, Pathologic / genetics
  • Neovascularization, Pathologic / immunology
  • Neovascularization, Pathologic / pathology
  • Nerve Tissue Proteins / genetics*
  • Nerve Tissue Proteins / pharmacology
  • Tumor Microenvironment / drug effects
  • Vascular Endothelial Growth Factor A / genetics*
  • Vascular Endothelial Growth Factor A / pharmacology

Substances

  • Antibodies, Monoclonal
  • Membrane Proteins
  • Nerve Tissue Proteins
  • SEMA3F protein, human
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A