Prostaglandin E2 produced by inducible COX-2 and mPGES-1 promoting cancer cell proliferation in vitro and in vivo.

Abstract

AIM:

Many cancers originate and flourish in a prolonged inflammatory environment. Our aim is to understand the mechanisms of how the pathway of prostaglandin E2 (PGE2) biosynthesis and signaling can promote cancer growth in inflammatory environment at cellular and animal model levels.

MAIN METHODS:

In this study, a chronic inflammation pathway was mimicked with a stable cell line that over-expressed a novel human enzyme consisting of cyclooxygenase isoform-2 (COX-2) linked to microsomal (PGE2 synthase-1 (mPGES-1)) for the overproduction of pathogenic PGE2. This PGE2-producing cell line was co-cultured and co-implanted with three human cancer cell lines including prostate, lung, and colon cancers in vitro and in vivo, respectively.

KEY FINDINGS:

Increases in cell doubling rates for the three cancer cell types in the presence of the PGE2-producing cell line were clearly observed. In addition, one of the four human PGE2 subtype receptors, EP1, was used as a model to identify PGE2-signaling involved in promoting the cancer cell growth. This finding was further proven in vivo by co-implanting the PGE2-producing cells line and the EP1-positive cancer cells into the immune deficient mice, after that, it was observed that the PGE2-producing cells promoted all three types of cancer formation in the mice.

SIGNIFICANCE:

This study clearly demonstrated that the human COX-2 linked to mPGES-1 is a pathway that, when mediated by the EP, is linked to promoting cancer growth in a chronic inflammatory environment. The identified pathway could be used as a novel target for developing and advancing anti-inflammation and anti-cancer interventions.

• Authors: Diana Ruan, Shui-Ping So
• Journal: Life sciences (Life Sci) Vol. 116 Issue 1 Pg. 43-50 (Oct 22 2014) ISSN: 1879-0631 [Electronic] Netherlands
• PMID: 25139833 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Inc. All rights reserved.

Chemical References

• Receptors, Prostaglandin E
• Cyclooxygenase 2
• PTGS2 protein, human
• Intramolecular Oxidoreductases
• PTGES protein, human
• Prostaglandin-E Synthases
• Ptges protein, mouse
• Dinoprostone

Topics

• Animals
• Cell Line, Tumor
• Cell Proliferation (physiology)
• Colonic Neoplasms (pathology)
• Cyclooxygenase 2 (metabolism)
• Dinoprostone (biosynthesis)
• Humans
• Inflammation (pathology)
• Intramolecular Oxidoreductases (metabolism)
• Lung Neoplasms (pathology)
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Microsomes (metabolism)
• Prostaglandin-E Synthases
• Prostatic Neoplasms (pathology)
• Receptors, Prostaglandin E (metabolism)