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Role of prostanoids in gastrointestinal cancer
Dingzhi Wang, Raymond N. DuBois
Dingzhi Wang, Raymond N. DuBois
Published May 7, 2018
Citation Information: J Clin Invest. 2018;128(7):2732-2742. https://doi.org/10.1172/JCI97953.
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Review Series

Role of prostanoids in gastrointestinal cancer

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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.

Authors

Dingzhi Wang, Raymond N. DuBois

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Figure 1

An overview of prostanoid synthesis pathways.

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An overview of prostanoid synthesis pathways.
Free arachidonic acid can ...
Free arachidonic acid can be metabolized to PGH2 by COX-1 and COX-2. NSAIDs inhibit activity of COX-1 and COX-2, whereas COXIBs inhibit activity of COX-2. PGH2 is sequentially metabolized to PGI2 by PTGIS, TxA2 by TBXAS1, PGE2 by PGES, PGF2α by PTGFS, and PGD2 by PTGDS. PGE2 binding at EP1–EP4 receptors is known to promote cancer development via multiple mechanisms (described in detail in the text and Figures 2 and 3). The roles of other prostanoids and their receptors in gastrointestinal cancer remain unclear (also detailed in the text).

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ISSN: 0021-9738 (print), 1558-8238 (online)

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