Emerging role of endothelin-1 in tumor angiogenesis

Trends Endocrinol Metab. 2003 Jan;14(1):44-50. doi: 10.1016/s1043-2760(02)00010-3.

Abstract

Tumor vessels express distinct molecular markers that are functionally relevant in the angiogenic process. Although tyrosine kinase receptor agonists are the major mediators of angiogenesis, several G-protein-coupled receptor agonists have also been shown to have a role. Among these, endothelin-1 (ET-1), by acting directly on endothelial cells via the ET(B) receptor, modulates different stages of neovascularization, including proliferation, migration, invasion, protease production and morphogenesis, and also stimulates neovascularization in vivo. ET-1 can also modulate tumor angiogenesis indirectly through the induction of vascular endothelial growth factor (VEGF). Engagement of the ET(A) receptor by ET-1 induces VEGF production by increasing levels of hypoxia-inducible factor 1 alpha. Moreover, tumor cells themselves, predominantly expressing the ET(A) receptor, might form vessel-like channels within the tumors. The role of ET-1 and its signaling network in tumor angiogenesis suggests that new therapeutic strategies using specific ET(A)-receptor antagonists could improve antitumor treatment by inhibiting both neovascularization and tumor cell growth.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • DNA-Binding Proteins / metabolism
  • Endothelial Growth Factors / metabolism*
  • Endothelin Receptor Antagonists
  • Endothelin-1 / metabolism*
  • Humans
  • Hypoxia-Inducible Factor 1
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Lymphokines / metabolism*
  • Neoplasms / blood supply*
  • Neoplasms / metabolism*
  • Neovascularization, Pathologic / metabolism*
  • Nuclear Proteins / metabolism
  • Receptor, Endothelin A
  • Receptor, Endothelin B
  • Receptors, Endothelin / metabolism*
  • Signal Transduction
  • Transcription Factors*
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors

Substances

  • DNA-Binding Proteins
  • Endothelial Growth Factors
  • Endothelin Receptor Antagonists
  • Endothelin-1
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Intercellular Signaling Peptides and Proteins
  • Lymphokines
  • Nuclear Proteins
  • Receptor, Endothelin A
  • Receptor, Endothelin B
  • Receptors, Endothelin
  • Transcription Factors
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors