Diana Ruan1, Shui-Ping So2. 1. I.I. Rabi Scholar Research Program, Columbia College, Columbia University, New York, NY 10027, USA. 2. Center for Experimental Therapeutics and Pharmacoinformatics, Department of Pharmacological and Pharmaceutical Sciences, University of Houston, Houston, TX 77204, USA. Electronic address: dtr2111@columbia.edu.
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.
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 humancancer 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 humanPGE2 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: Jonathan G Hiller; Nicholas J Perry; George Poulogiannis; Bernhard Riedel; Erica K Sloan Journal: Nat Rev Clin Oncol Date: 2017-12-28 Impact factor: 66.675
Authors: Luke V Selby; Ana Fernandez-Bustamante; Aslam Ejaz; Ana Gleisner; Timothy M Pawlik; David J Douin Journal: J Gastrointest Surg Date: 2021-06-07 Impact factor: 3.267