Understanding the tumour micro-environment communication network from an NOS2/COX2 perspective

Br J Pharmacol. 2019 Jan;176(2):155-176. doi: 10.1111/bph.14488. Epub 2018 Nov 6.

Abstract

Recent findings suggest that co-expression of NOS2 and COX2 is a strong prognostic indicator in triple-negative breast cancer patients. These two key inflammation-associated enzymes are responsible for the biosynthesis of NO and PGE2 , respectively, and can exert their effect in both an autocrine and paracrine manner. Impairment of their physiological regulation leads to critical changes in both intra-tumoural and intercellular communication with the immune system and their adaptation to the hypoxic tumour micro-environment. Recent studies have also established a key role of NOS2-COX2 in causing metabolic shift. This review provides an extensive overview of the role of NO and PGE2 in shaping communication between the tumour micro-environment composed of tumour and immune cells that in turn favours tumour progression and metastasis. LINKED ARTICLES: This article is part of a themed section on Nitric Oxide 20 Years from the 1998 Nobel Prize. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.2/issuetoc.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Review

MeSH terms

  • Animals
  • Cyclooxygenase 2 / metabolism*
  • Humans
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type II / metabolism*
  • Tumor Microenvironment

Substances

  • Nitric Oxide
  • Nitric Oxide Synthase Type II
  • Cyclooxygenase 2