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Prostaglandin E2/EP Signaling in the Tumor Microenvironment of Colorectal Cancer

The number of colorectal cancer (CRC) patients is increasing worldwide. Accumulating evidence has shown that the tumor microenvironment (TME), including macrophages, neutrophils, and fibroblasts, plays an important role in the development and progression of CRC. Although targeting the TME could be a...

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Detalles Bibliográficos
Autores principales: Mizuno, Rei, Kawada, Kenji, Sakai, Yoshiharu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6940958/
https://www.ncbi.nlm.nih.gov/pubmed/31835815
http://dx.doi.org/10.3390/ijms20246254
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author Mizuno, Rei
Kawada, Kenji
Sakai, Yoshiharu
author_facet Mizuno, Rei
Kawada, Kenji
Sakai, Yoshiharu
author_sort Mizuno, Rei
collection PubMed
description The number of colorectal cancer (CRC) patients is increasing worldwide. Accumulating evidence has shown that the tumor microenvironment (TME), including macrophages, neutrophils, and fibroblasts, plays an important role in the development and progression of CRC. Although targeting the TME could be a promising therapeutic approach, the mechanisms by which inflammatory cells promote CRC tumorigenesis are not well understood. When inflammation occurs in tissues, prostaglandin E2 (PGE2) is generated from arachidonic acid by the enzyme cyclooxygenase-2 (COX-2). PGE2 regulates multiple functions in various immune cells by binding to the downstream receptors EP1, EP2, EP3, and EP4, and plays an important role in the development of CRC. The current therapies targeting PGE2 using non-steroidal anti-inflammatory drugs (NSAIDs) or COX-2 inhibitors have failed due to the global prostanoid suppression resulting in the severe adverse effects despite the fact they could prevent tumorigenesis. Therefore, therapies targeting the specific downstream molecules of PGE2 signaling could be a promising approach. This review highlights the role of each EP receptor in the TME of CRC tumorigenesis and their therapeutic potential.
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spelling pubmed-69409582020-01-09 Prostaglandin E2/EP Signaling in the Tumor Microenvironment of Colorectal Cancer Mizuno, Rei Kawada, Kenji Sakai, Yoshiharu Int J Mol Sci Review The number of colorectal cancer (CRC) patients is increasing worldwide. Accumulating evidence has shown that the tumor microenvironment (TME), including macrophages, neutrophils, and fibroblasts, plays an important role in the development and progression of CRC. Although targeting the TME could be a promising therapeutic approach, the mechanisms by which inflammatory cells promote CRC tumorigenesis are not well understood. When inflammation occurs in tissues, prostaglandin E2 (PGE2) is generated from arachidonic acid by the enzyme cyclooxygenase-2 (COX-2). PGE2 regulates multiple functions in various immune cells by binding to the downstream receptors EP1, EP2, EP3, and EP4, and plays an important role in the development of CRC. The current therapies targeting PGE2 using non-steroidal anti-inflammatory drugs (NSAIDs) or COX-2 inhibitors have failed due to the global prostanoid suppression resulting in the severe adverse effects despite the fact they could prevent tumorigenesis. Therefore, therapies targeting the specific downstream molecules of PGE2 signaling could be a promising approach. This review highlights the role of each EP receptor in the TME of CRC tumorigenesis and their therapeutic potential. MDPI 2019-12-11 /pmc/articles/PMC6940958/ /pubmed/31835815 http://dx.doi.org/10.3390/ijms20246254 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Mizuno, Rei
Kawada, Kenji
Sakai, Yoshiharu
Prostaglandin E2/EP Signaling in the Tumor Microenvironment of Colorectal Cancer
title Prostaglandin E2/EP Signaling in the Tumor Microenvironment of Colorectal Cancer
title_full Prostaglandin E2/EP Signaling in the Tumor Microenvironment of Colorectal Cancer
title_fullStr Prostaglandin E2/EP Signaling in the Tumor Microenvironment of Colorectal Cancer
title_full_unstemmed Prostaglandin E2/EP Signaling in the Tumor Microenvironment of Colorectal Cancer
title_short Prostaglandin E2/EP Signaling in the Tumor Microenvironment of Colorectal Cancer
title_sort prostaglandin e2/ep signaling in the tumor microenvironment of colorectal cancer
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6940958/
https://www.ncbi.nlm.nih.gov/pubmed/31835815
http://dx.doi.org/10.3390/ijms20246254
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