COMPORTAMENTO DA PROSTAGLANDINA E2 NO MICROAMBIENTE TUMORAL E SEU IMPACTO NAS CÉLULAS DENDRÍTICAS: UMA REVISÃO INTEGRATIVA
DOI:
https://doi.org/10.18554/acbiobras.v7i2.8046Keywords:
Prostaglandina E2, Câncer, Células dendríticasAbstract
Esta revisão integrativa fornece uma análise aprofundada da influência da prostaglandina E2 no ambiente intratumoral, destacando sua associação com formas de evasão imunológica. Os estudos revistos revelam que a presença, o comportamento e a sobre-expressão da PGE2 são cruciais na formação do microambiente tumoral, enfatizando a necessidade de uma compreensão mais detalhada destas interações. Vários estudos têm enfatizado a importância da investigação de agentes capazes de modular citocinas e quimiocinas no microambiente tumoral, bem como o uso da imunoterapia como abordagens promissoras para o tratamento de condições imunometabólicas específicas. Essas alternativas visam fortalecer o sistema imunológico do hospedeiro contra as células tumorais, representando uma estratégia esperançosa para superar as barreiras de imunossupressão associadas a moléculas como a prostaglandina E2. Portanto, esta revisão destaca a complexidade das interações entre PGE2, células dendríticas e câncer, indicando caminhos promissores para futuras investigações e intervenções terapêuticas mais direcionadas e eficazes.
References
Palucka AK, Coussens LM. The Basis of Oncoimmunology. Cell. 2016; 164(6): 1233-1247. doi: 10.1016/j.cell.2016.01.049.
Wong CC, Kang W, Xu J, Qian Y, Luk STY, Chen H, Li W, Zhao L, Zhang X, Chiu PW, Ng EK, Yu J. Prostaglandin E 2 induces DNA hypermethylation in gastric cancer in vitro and in vivo. Theranostics. 2019;9(21):6256-6268. doi:10.7150/thno.35766.
Harris SG, Padilla J, Koumas L, Ray D, Phipps RP. Prostaglandins as modulators of immunity. Trends Immunol. 2002;23(3):144-150. doi:10.1016/S1471-4906(01)02154-8.
Wang Q, Morris RJ, Bode AM, Zhang T. Prostaglandin Pathways: Opportunities for Cancer Prevention and Therapy. Cancer Res. 2022;82(6):949-965. doi:10.1158/0008-5472.CAN-21-2297/674402/AM/PROSTAGLANDIN-PATHWAYS-OPPORTUNITIES-FOR-CANCER.
Finetti F, Travelli C, Ercoli J, Colombo G, Buoso E, Trabalzini L. Prostaglandin E2 and Cancer: Insight into Tumor Progression and Immunity. Biology (Basel). 2020;9(12):434. doi:10.3390/biology9120434.
Echizen K, Oshima H, Nakayama M, Oshima M. The inflammatory microenvironment that promotes gastrointestinal cancer development and invasion. Adv Biol Regul. 2018;68:39-45. doi:10.1016/j.jbior.2018.02.001.
Osawa K, Umemura M, Nakakaji R, Tanaka R, Islam RM, Nagasako A, Fujita T, Yokoyama U, Koizumi T, Mitsudo K, Ishikama Y. Prostaglandin E 2 receptor EP4 regulates cell migration through Orai1. Cancer Sci. 2020;111(1):160-174. doi:10.1111/cas.14247.
Aoki T, Narumiya S. Prostaglandin E2-EP2 signaling as a node of chronic inflammation in the colon tumor microenvironment. Inflamm Regen. 2017;37(1):4. doi:10.1186/s41232-017-0036-7.
Asting AG, Iresjö BM, Nilsberth C, Smedh U, Lundholm K. Host knockout of E-prostanoid 2 receptors reduces tumor growth and causes major alterations of gene expression in prostaglandin E2-producing tumors. Oncol Lett. 2017;13(1):476-482. doi:10.3892/ol.2016.5448.
Böttcher JP, Bonavita E, Chakravarty P, Blees H, Cabeza-Cabrerizo M, Sammicheli S, Rogers NC, Sahai E, Zelenay S, Reis e Sousa C. NK Cells Stimulate Recruitment of cDC1 into the Tumor Microenvironment Promoting Cancer Immune Control. Cell. 2018;172(5):1022-1037.e14. doi:10.1016/j.cell.2018.01.004.
Watanabe K, Tominari T, Hirata M, Matsumoto C, Maruyama T, Murphy G, Nagase H, Miyaura C, Inada M. Abrogation of prostaglandin E-EP4 signaling in osteoblasts prevents the bone destruction induced by human prostate cancer metastases. Biochem Biophys Res Commun. 2016;478(1):154-161. doi:10.1016/j.bbrc.2016.07.075.
Xie C, Xu X, Wang X, Wei S, Shao L, Chen J, Cai J, Jia L. Cyclooxygenase 2 induces angiogenesis in pancreatic cancer mediated by prostaglandin E2. Oncol Lett. Published online May 22, 2018. doi:10.3892/ol.2018.8786
Nandi P, Girish G V., Majumder M, Xin X, Tutunea-fatan E, Lala PK. PGE2 promotes breast cancer-associated lymphangiogenesis by activation of EP4 receptor on lymphatic endothelial cells. BMC Cancer. 2017;17(1):11. doi:10.1186/s12885-016-3018-2.
Pandey VK, Amin PJ, Shankar BS. COX-2 inhibitor prevents tumor induced down regulation of classical DC lineage specific transcription factor Zbtb46 resulting in immunocompetent DC and decreased tumor burden. Immunol Lett. 2017;184:23-33. doi:10.1016/j.imlet.2017.01.019.
Kashiwagi E, Inoue S, Mizushima T, Chen J, Ide H, Kawahara T, Reis LO, Baras AS, Netto GJ, Miyamoto H.Prostaglandin receptors induce urothelial tumourigenesis as well as bladder cancer progression and cisplatin resistance presumably via modulating PTEN expression. Br J Cancer. 2018;118(2):213-223. doi:10.1038/bjc.2017.393.
Rong Y, Yuan CH, Qu Z, Zhou H, Guan Q, Yang N, Leng XH, Bu L, Wu K, Wang FB. Doxorubicin resistant cancer cells activate myeloid-derived suppressor cells by releasing PGE2. Sci Rep. 2016;6(1):23824. doi:10.1038/srep23824.
Saha J, Sarkar D, Pramanik A, Mahanti K, Adhikary A, Bhattacharyya S. PGE2-HIF1? reciprocal induction regulates migration, phenotypic alteration and immunosuppressive capacity of macrophages in tumor microenvironment. Life Sci. 2020;253:117731. doi:10.1016/j.lfs.2020.117731.
Take Y, Koizumi S, Nagahisa A. Prostaglandin E Receptor 4 Antagonist in Cancer Immunotherapy: Mechanisms of Action. Front Immunol. 2020;11. doi:10.3389/fimmu.2020.00324.
Tönisen F, Perrin L, Bayarmagnai B, Van den dries K, Cambi A, Gligorijevic B. EP4 receptor promotes invadopodia and invasion in human breast cancer. Eur J Cell Biol. 2017;96(2):218-226. doi:10.1016/j.ejcb.2016.12.005.
Zhang Y, Purayil HT, Black JB, Fetto F, Lynch LD, Masannat JN, Daaka Y. Prostaglandin E2 receptor 4 mediates renal cell carcinoma intravasation and metastasis. Cancer Lett. 2017;391:50-58. doi:10.1016/j.canlet.2017.01.007.
Bellamkonda K, Chandrashekar NK, Osman J, Selvanesan BC, Savari S, Sjölander A. The eicosanoids leukotriene D4 and prostaglandin E2 promote the tumorigenicity of colon cancer-initiating cells in a xenograft mouse model. BMC Cancer. 2016;16(1):425. doi:10.1186/s12885-016-2466-z.
Kim HB, Kim M, Park YS, Park I, Kim T, Yang SY, Cho CJ, Hwang D, Jung JH, Markowitz SD, Hwang SW, Yang SK, Lim DS, Myung SJ. Prostaglandin E2 Activates YAP and a Positive-Signaling Loop to Promote Colon Regeneration After Colitis but Also Carcinogenesis in Mice. Gastroenterology. 2017;152(3):616-630. doi:10.1053/j.gastro.2016.11.005.
Porta C, Consonni FM, Morlacchi S, Sangaletti S, Bleve A, Totaro MG, Larghi P, Rimoldi M, Tripodo C, Strauss L, Banfi S, Storto M, Pressiani T, Rimassa L, Tartari S, Ippolito A, Doni A, Soldà G, Duga S, Piccolo V, Ostuni R, Natoli G, Bronte V, Balzac F, Turco E, Hirsch E, Colombo MP, Sica A. . Tumor-Derived Prostaglandin E2 Promotes p50 NF-?B-Dependent Differentiation of Monocytic MDSCs. Cancer Res. 2020;80(13):2874-2888. doi:10.1158/0008-5472.CAN-19-2843.
Schumacher Y, Aparicio T, Ourabah S, Baraille F, Martin A, Wind P, Dentin R, Postic C, Guilmeau S. Dysregulated CRTC1 activity is a novel component of PGE2 signaling that contributes to colon cancer growth. Oncogene. 2016;35(20):2602-2614. doi:10.1038/onc.2015.283.
Calder PC. Eicosanoids. Essays Biochem. 2020;64(3):423-441. doi:10.1042/EBC20190083
Wang D, Dubois RN. Eicosanoids and cancer. Nat Rev Cancer. 2010;10(3):181-193. doi:10.1038/nrc2809.
Ching MM, Reader J, Fulton AM. Eicosanoids in Cancer: Prostaglandin E2 Receptor 4 in Cancer Therapeutics and Immunotherapy. Front Pharmacol. 2020;11. doi:10.3389/fphar.2020.00819.
Bayerl F, Meiser P, Donakonda S, Hirschberger A, Lacher SB, Pedde AM, Hermann CD, Elewaut A, Knolle M, Ramsauer L, Rudolph TJ, Grassmann S, Öllinger R, Kirchhammer N, Trefny M, Anton M, Wohlleber D, Höchst B, Zaremba A, Krüger A, Rad R, Obenauf AC, Schadendorf D, Zippelius A, Buchholz VR, Schraml BU, Böttcher JP. Tumor-derived prostaglandin E2 programs cDC1 dysfunction to impair intratumoral orchestration of anti-cancer T cell responses. Immunity. 2023; 56(6):1341-1358.e11. doi:10.1016/j.immuni.2023.05.011.
Semmlinger A, von Schoenfeldt V, Wolf V, Meuter A, Kolben TM, Kolben T, Zeder-Goess C, Weis F, Gallwas J, Wuerstlein R, Hermelink K, Schmoeckel E, Harbeck N, Mayr D, Mahner S, Jeschke U, Ditsch N. EP3 (prostaglandin E2 receptor 3) expression is a prognostic factor for progression-free and overall survival in sporadic breast cancer. BMC Cancer. 2018;18(1):431. doi:10.1186/s12885-018-4286-9.
