title: Role of inflammation and inflammatory mediators in colorectal cancer.
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.
authors.forename: Raymond N
authors.initials: RN
authors.lastname: Dubois
mesh_terms: D000236:Adenoma / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D001397:Azoxymethane; D003092:Colitis / Q000139:chemically induced / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D003106:Colon / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D015179:Colorectal Neoplasms / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016264:Dextran Sulfate; D015232:Dinoprostone / Q000378:metabolism; D004195:Disease Models, Animal; D017491:Genes, APC; D006801:Humans; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D051381:Rats; D023063:Receptors, Interleukin-8B / Q000172:deficiency / Q000235:genetics / Q000378:metabolism
chemical_list: D018836:Inflammation Mediators; D023063:Receptors, Interleukin-8B; D016264:Dextran Sulfate; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; C489691:Ptgs2 protein, rat; D015232:Dinoprostone; D001397:Azoxymethane