Recombinant disintegrin targets α(v) β(3) integrin and leads to mediator production

Cell Adh Migr. 2014;8(1):60-5. doi: 10.4161/cam.27698. Epub 2013 Jan 1.

Abstract

Integrin αvβ3 is most likely the foremost modulator of angiogenesis among all known integrins. Recombinant disintegrin DisBa-01, originally obtained from snake venom glands, binds to αvβ3, thereby significantly inhibiting adhesion and generating in vivo anti-metastatic ability. However, its function in mediator production is not clear. Here, we observed that the mediators VEGF-A, IL-8, and TGF-β are not produced by human umbilical vein endothelial cells (HUVEC cell line) or monocyte/macrophage cells (SC cell line) when cells adhered to vitronectin. However, when exposed to DisBa-01, HUVECs produced higher levels of TGF-β, and SC cells produced higher levels of VEGF-A. Nonetheless, HUVECs also showed an enhancement of apoptosis after losing adherence when exposed to disintegrin, which is a characteristic of anoikis. We propose that disintegrin DisBa-01 could be used to modulate integrin αvβ3 functions.

Keywords: DisBa; HUVEC; IL-8; TGF; VEGF; cancer; endothelial cell; integrin αvβ3; macrophage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / pharmacology*
  • Apoptosis / drug effects
  • Cell Adhesion
  • Cell Survival / drug effects
  • Cells, Cultured
  • Cytokines / biosynthesis*
  • Disintegrins / pharmacology*
  • Drug Screening Assays, Antitumor
  • Human Umbilical Vein Endothelial Cells / drug effects
  • Human Umbilical Vein Endothelial Cells / physiology
  • Humans
  • Integrin alphaVbeta3 / metabolism*
  • Recombinant Proteins / pharmacology
  • Vitronectin / metabolism

Substances

  • Angiogenesis Inhibitors
  • Cytokines
  • Disintegrins
  • Integrin alphaVbeta3
  • Recombinant Proteins
  • Vitronectin