Exosomes in Angiogenesis and Anti-angiogenic Therapy in Cancers

Int J Mol Sci. 2020 Aug 14;21(16):5840. doi: 10.3390/ijms21165840.

Abstract

Angiogenesis is the process through which new blood vessels are formed from pre-existing ones. Exosomes are involved in angiogenesis in cancer progression by transporting numerous pro-angiogenic biomolecules like vascular endothelial growth factor (VEGF), matrix metalloproteinases (MMPs), and microRNAs. Exosomes promote angiogenesis by suppressing expression of factor-inhibiting hypoxia-inducible factor 1 (HIF-1). Uptake of tumor-derived exosomes (TEX) by normal endothelial cells activates angiogenic signaling pathways in endothelial cells and stimulates new vessel formation. TEX-driven cross-talk of mesenchymal stem cells (MSCs) with immune cells blocks their anti-tumor activity. Effective inhibition of tumor angiogenesis may arrest tumor progression. Bevacizumab, a VEGF-specific antibody, was the first antiangiogenic agent to enter the clinic. The most important clinical problem associated with cancer therapy using VEGF- or VEFGR-targeting agents is drug resistance. Combined strategies based on angiogenesis inhibitors and immunotherapy effectively enhances therapies in various cancers, but effective treatment requires further research.

Keywords: angiogenesis; anti-angiogenic therapy; exosomes; extracellular vesicles.

Publication types

  • Review

MeSH terms

  • Angiogenesis Inhibitors / therapeutic use*
  • Animals
  • Endothelial Cells / metabolism
  • Endothelial Cells / pathology
  • Exosomes / metabolism*
  • Humans
  • Neoplasms / blood supply*
  • Neoplasms / drug therapy*
  • Neovascularization, Pathologic / drug therapy*
  • Randomized Controlled Trials as Topic

Substances

  • Angiogenesis Inhibitors