Role of prostanoids in gastrointestinal cancer

Abstract

Chronic inflammation is a risk factor for gastrointestinal cancer and other diseases. Most studies have focused on cytokines and chemokines as mediators connecting chronic inflammation to cancer, whereas the involvement of lipid mediators, including prostanoids, has not been extensively investigated. Prostanoids are among the earliest signaling molecules released in response to inflammation. Multiple lines of evidence suggest that prostanoids are involved in gastrointestinal cancer. In this Review, we discuss how prostanoids impact gastrointestinal cancer development. In particular, we highlight recent advances in our understanding of how prostaglandin E2 induces the immunosuppressive microenvironment in gastrointestinal cancers.

Preoperative stimulation of resolution and inflammation blockade eradicates micrometastases

“…Thus, COX-2 inhibitors may be "resolution toxic," as they suppress the production of these prostaglandins (12,39,40,43) and may worsen therapy-induced cancer progression. PGE 2 also exhibits immunosuppressive activity, stimulates regulatory T cells, inhibits antigen presentation, and suppresses NK cells (36,38). Although these functions demonstrate the role of PGE 2 in the resolution phase of inflammation, they may inhibit antitumor immunity, hence promoting tumor escape (36).…”

“…Chronic inflammation has been associated with tumor-promoting activity (36,37), in part due to a deficit in the resolution of inflammation (12). Cancer therapies have focused on blocking the production of COX-2-derived eicosanoids to suppress tumor-promoting inflammation (38).…”

“…PGE 2 also exhibits immunosuppressive activity, stimulates regulatory T cells, inhibits antigen presentation, and suppresses NK cells (36,38). Although these functions demonstrate the role of PGE 2 in the resolution phase of inflammation, they may inhibit antitumor immunity, hence promoting tumor escape (36). The dual activities of eicosanoids may explain the biphasic dose-dependent or paradoxical relationship between chronic use of NSAIDs and cancer risk (44).…”

“…Inflammation plays a multifaceted role in regulating the adaptive immune response. For example, prostaglandins, such as PGE 2 , suppress acute inflammatory mediators, activate dendritic cells, sensitize T cells to eliminate infection, and promote T cell exhaustion (36,42). Moreover, adaptive antitumor immunity has been implicated in the regulation of metastatic tumor dormancy (63,64).…”

Altered Structural Expression and Enzymatic Activity Parameters in Quiescent Ulcerative Colitis: Are These Potential Normalization Criteria?

“…It is important to gain further information on PGE 2 receptors, as they mediate PGE 2 effects in acute inflammation and are associated with the development of colorectal cancer as well as other serious complications related to IBD [18,30]. The application of exogenous PGE 2 provided data indicating the presence of two distinct functional PGE 2 receptors, a high-and a low-affinity receptor.…”