Work

Role of inflammation and inflammatory mediators in colorectal cancer.

Year: 2014

Type: article

Abstract: Chronic inflammation is a risk factor for several different cancers including colorectal cancer (CRC). However, the mechanisms underlying the contribution of inflammation to cancer remain elusive. Pro-inflammatory mediators such as cyclooxygenase 2 (COX-2) and prostaglandin E2 (PGE2) contribute to cancer progression. Here, we show that COX-2 is an immediate-early response gene induced by growth factors and pro-inflammatory cytokines and its levels are elevated in human CRCs. Furthermore, we show that COX-2-derived PGE2 promotes colonic tumor growth via silencing certain tumor suppressors and DNA repair genes by DNA methylation in colonic epithelial tumor cells. We also report that C-X-C motif chemokine receptor 2 accelerates colonic inflammation and colitis-associated tumorigenesis by mediating myeloid-derived suppressor cell recruitment to the tumor microenvironment. These findings not only support a rationale to target these pro-inflammatory pathways for cancer prevention and treatment but also provide support for developing new therapeutic approaches to subvert chronic inflammation- and tumor-induced immunosuppression.

Source: PubMed

Author: Raymond N Dubois

Institution: Arizona State University

Language: English

Topic: Inflammatory mediators and NSAID effects

Subfield: Pharmacology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: green

Funders: National Institutes of Health, National Cancer Institute, National Institute of Diabetes and Digestive and Kidney Diseases

Awards: Nuclear Hormone Receptor in Intestinal Biology, Role of Eicosanoids in Intestinal Biology, The Role of Bioactive Lipids in Inflammation and Cancer, Eicosanoids and Intestinal Epithelial Growth Regulation, (PQA1)The Molecular Mechanisms Underlying Effects of Aspirin on Colorectal Cancer