Emerging role of endothelin-1 in tumor angiogenesis

Anna Bagnato, Francesca Spinella

Research output: Contribution to journalArticle

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-proteincoupled receptor agonists have also been shown to have a role. Among these, endothelin-1 (ET-1), by acting directly on endothelial cells via the ETB 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 ETA receptor by ET-1 induces VEGF production by increasing levels of hypoxia-inducible factor 1α. Moreover, tumor cells themselves, predominantly expressing the ETA 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 ETA-receptor antagonists could improve antitumor treatment by inhibiting both neovascularization and tumor cell growth.

Original languageEnglish
Pages (from-to)44-50
Number of pages7
JournalTrends in Endocrinology and Metabolism
Volume14
Issue number1
DOIs
Publication statusPublished - Jan 2003

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

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