An Inflammatory Mediator, Prostaglandin E2, in Colorectal Cancer

Abstract

It is widely accepted that dietary fats and chronic inflammation are risk factors for developing colorectal cancer. Arachidonic acid is a major component of animal fats and the bioactive lipids produced from this substrate play critical roles in a variety of biologic processes, including cancer. Cyclooxygenase-derived prostaglandin E 2 (PGE 2 ) is a known pro-inflammatory lipid mediator and promotes tumor progression. Metabolism of arachidonic acid by the cyclooxygenase pathway provides one mechanism for the contribution of dietary fats and chronic inflammation to carcinogenesis. In this review, we highlight recent advances in our understanding of how proinflammatory mediator PGE 2 promotes colorectal cancer immune evasion. These findings may provide a rationale for the development of new therapeutic approaches to subvert tumor-induced immunosuppression.

Cytosolic phospholipase A2: physiological function and role in disease

“…Although results support a role for PGs in protecting the integrity of the intestine, COX-2 expression and PGE 2 -mediated infl ammation are associated with development of human colorectal cancer, consistent with epidemiological evidence that nonsteroid anti-infl ammatory drug use is protective (128)(129)(130). However, cPLA 2 2 ␣ , but decidualization is unaffected ( 151 ).…”

FosB transcription factor regulates COX-2 expression in colorectal cancer cells without affecting PGE2 expression

“…In previous studies by the present authors, increased COX-2 staining was able to predict tumor tissue content of PGE2 in CRC patients, while COX-1 staining had an inverse correlation with PGE2 content (14,15). Furthermore, PGE2 levels were observed to be increased in premalignant adenomatous polyps and colon cancer tissues, compared with normal controls (16,17).…”

“…Cells were maintained in a humidified incubator at 37˚C and 5% CO 2 . Early passages (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17) were used for the experiments.…”

The Pharmacological and Physiological Role of Multidrug-Resistant Protein 4

“…COX2-PGE 2 signaling is highly activated in numerous cancers, especially lung (Furugen et al, 2013) and colon cancer (Park et al, 2011), and in situations of abundant intracellular accumulation PGE 2 can be extruded by MRP4. The continuous elevated extracellular PGE 2 can shift the tumor microenvironment from antitumor to immunosuppressive responses, resulting in escape of tumor cells from effective immunosurveillance (Wang and DuBois, 2013). It has been shown that PGE 2 can downregulate tumor immunity through inhibiting dendritic cell (DC) differentiation and switching the function of DCs from induction of immunity to T-cell tolerance (Chinen et al, 2011); inhibiting CD8 1 T-cell proliferation and activity (Ganapathy et al, 2000); the inhibition of mature B-cell proliferation and induction of immature B-cell apoptosis (Shimozato and Kincade, 1999); downregulation of antitumor TH1 cytokines and upregulation of immunosuppressive TH2 cytokines (Fabricius et al, 2010); and inducing myeloid-derived suppressor cell differentiation (Sinha et al, 2007).…”