Multifaceted roles of PGE2 in inflammation and cancer

Abstract

Prostaglandin E2 (PGE2) is a bioactive lipid that elicits a wide range of biological effects associated with inflammation and cancer. PGE2 exerts diverse effects on cell proliferation, apoptosis, angiogenesis, inflammation and immune surveillance. This review concentrates primarily on gastrointestinal cancers, where the actions of PGE2 are most prominent, most likely due to the constant exposure to dietary and environmental insults and the intrinsic role of PGE2 in tissue homeostasis. A discussion of recent efforts to elucidate the complex and interconnected pathways that link PGE2 signaling with inflammation and cancer is provided, supported by the abundant literature showing a protective effect of NSAIDs and the therapeutic efficacy of targeting mPGES-1 or EP receptors for cancer prevention. However, suppressing PGE2 formation as a means of providing chemoprotection against all cancers may not ultimately be tenable, undoubtedly the situation for patients with inflammatory bowel disease. Future studies to fully understand the complex role of PGE2 in both inflammation and cancer will be required to develop novel strategies for cancer prevention that are both effective and safe.

Human mast cells promote colon cancer growth via bidirectional crosstalk: studies in 2D and 3D coculture models

“…Besides, PGE 2 induces activation and expansion of both Tregs and MDSC (myeloid-derived suppressor cells) and thus supports immunosuppression in cancer milieu. 60 Human MC express multiple PGE2 receptors EP(2–4) with major expression of EP2 and EP3. 61 EP2 and EP4 have been reported as inhibitory receptors for MC activation.…”

COX2 and PGE2 mediate EGF-induced E-cadherin-independent human ovarian cancer cell invasion

“…PGE2 is the most common PG derived from COX2 (Nakanishi & Rosenberg 2013). To determine whether EGF-induced COX2 expression contributes to the production of PGE2, we measured PGE2 protein levels in the culture medium by ELISA after 1, 3, and 6 h of EGF treatment.…”

“…PGE2 is an important PG that acts in an autocrine/paracrine manner to regulate various physiological and pathological functions (Nakanishi & Rosenberg 2013). Two isoforms of COX, COX1 and COX2, have been described.…”

Decursinol angelate inhibits PGE2-induced survival of the human leukemia HL-60 cell line via regulation of the EP2 receptor and NFκB pathway

“…3 Studies have shown that PGE 2 promotes tumor development by enhancing cell proliferation and survival, inflammation, angiogenesis, and invasiveness in various cancers. [4][5] The PGE 2 receptors EP1 and EP2 have been demonstrated to participate in PGE 2 -induced tumorigenesis as well as in PGE 2 -mediated cancer cell survival and protection from druginduced apoptosis, via the activation of cyclic adenosine monophosphate (cAMP)-dependent protein kinase A (PKA). 6,7 PGE 2 has been shown to significantly increase promonocytic cell proliferation and COX-2 expression, and this effect is mediated, at least in part, by the activation of the Ras/Raf/Erk signaling cascade.…”