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Erschienen in: Seminars in Immunopathology 2/2013

01.03.2013 | Review

Multifaceted roles of PGE2 in inflammation and cancer

verfasst von: Masako Nakanishi, Daniel W. Rosenberg

Erschienen in: Seminars in Immunopathology | Ausgabe 2/2013

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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.
Literatur
1.
Zurück zum Zitat Dong M, Guda K, Nambiar PR, Rezaie A, Belinsky GS et al (2003) Inverse association between phospholipase A2 and COX-2 expression during mouse colon tumorigenesis. Carcinogenesis 24(2):307–315PubMedCrossRef Dong M, Guda K, Nambiar PR, Rezaie A, Belinsky GS et al (2003) Inverse association between phospholipase A2 and COX-2 expression during mouse colon tumorigenesis. Carcinogenesis 24(2):307–315PubMedCrossRef
2.
Zurück zum Zitat Dong M, Johnson M, Rezaie A, Ilsley JN, Nakanishi M, et al. (2005) Cytoplasmic phospholipase A2 levels correlate with apoptosis in human colon tumorigenesis. Clin Cancer Res 11(6):2265–71 Dong M, Johnson M, Rezaie A, Ilsley JN, Nakanishi M, et al. (2005) Cytoplasmic phospholipase A2 levels correlate with apoptosis in human colon tumorigenesis. Clin Cancer Res 11(6):2265–71
3.
Zurück zum Zitat Ilsley JN, Nakanishi M, Flynn C, Belinsky GS, De Guise S et al (2005) Cytoplasmic phospholipase A2 deletion enhances colon tumorigenesis. Cancer Res 65(7):2636–2643PubMedCrossRef Ilsley JN, Nakanishi M, Flynn C, Belinsky GS, De Guise S et al (2005) Cytoplasmic phospholipase A2 deletion enhances colon tumorigenesis. Cancer Res 65(7):2636–2643PubMedCrossRef
5.
Zurück zum Zitat Funk CD (2001) Prostaglandins and leukotrienes: advances in eicosanoid biology. Science 294(5548):1871–1875PubMedCrossRef Funk CD (2001) Prostaglandins and leukotrienes: advances in eicosanoid biology. Science 294(5548):1871–1875PubMedCrossRef
6.
Zurück zum Zitat Smith WL (1989) The eicosanoids and their biochemical mechanisms of action. Biochem J 259(2):315–324PubMed Smith WL (1989) The eicosanoids and their biochemical mechanisms of action. Biochem J 259(2):315–324PubMed
7.
Zurück zum Zitat Wang D, Mann JR, DuBois RN (2005) The role of prostaglandins and other eicosanoids in the gastrointestinal tract. Gastroenterology 128(5):1445–1461PubMedCrossRef Wang D, Mann JR, DuBois RN (2005) The role of prostaglandins and other eicosanoids in the gastrointestinal tract. Gastroenterology 128(5):1445–1461PubMedCrossRef
8.
Zurück zum Zitat Jakobsson PJ, Thoren S, Morgenstern R, Samuelsson B (1999) Identification of human prostaglandin E synthase: a microsomal, glutathione-dependent, inducible enzyme, constituting a potential novel drug target. Proc Natl Acad Sci U S A 96(13):7220–7225PubMedCrossRef Jakobsson PJ, Thoren S, Morgenstern R, Samuelsson B (1999) Identification of human prostaglandin E synthase: a microsomal, glutathione-dependent, inducible enzyme, constituting a potential novel drug target. Proc Natl Acad Sci U S A 96(13):7220–7225PubMedCrossRef
9.
Zurück zum Zitat Murakami M, Naraba H, Tanioka T, Semmyo N, Nakatani Y et al (2000) Regulation of prostaglandin E2 biosynthesis by inducible membrane-associated prostaglandin E2 synthase that acts in concert with cyclooxygenase-2. J Biol Chem 275(42):32783–32792PubMedCrossRef Murakami M, Naraba H, Tanioka T, Semmyo N, Nakatani Y et al (2000) Regulation of prostaglandin E2 biosynthesis by inducible membrane-associated prostaglandin E2 synthase that acts in concert with cyclooxygenase-2. J Biol Chem 275(42):32783–32792PubMedCrossRef
10.
Zurück zum Zitat Tai HH, Cho H, Tong M, Ding Y (2006) NAD+-linked 15-hydroxyprostaglandin dehydrogenase: structure and biological functions. Curr Pharm Des 12(8):955–962PubMedCrossRef Tai HH, Cho H, Tong M, Ding Y (2006) NAD+-linked 15-hydroxyprostaglandin dehydrogenase: structure and biological functions. Curr Pharm Des 12(8):955–962PubMedCrossRef
11.
Zurück zum Zitat Yan M, Rerko RM, Platzer P, Dawson D, Willis J et al (2004) 15-Hydroxyprostaglandin dehydrogenase, a COX-2 oncogene antagonist, is a TGF-beta-induced suppressor of human gastrointestinal cancers. Proc Natl Acad Sci U S A 101(50):17468–17473PubMedCrossRef Yan M, Rerko RM, Platzer P, Dawson D, Willis J et al (2004) 15-Hydroxyprostaglandin dehydrogenase, a COX-2 oncogene antagonist, is a TGF-beta-induced suppressor of human gastrointestinal cancers. Proc Natl Acad Sci U S A 101(50):17468–17473PubMedCrossRef
12.
Zurück zum Zitat Backlund MG, Mann JR, Holla VR, Buchanan FG, Tai HH et al (2005) 15-Hydroxyprostaglandin dehydrogenase is down-regulated in colorectal cancer. J Biol Chem 280(5):3217–3223PubMedCrossRef Backlund MG, Mann JR, Holla VR, Buchanan FG, Tai HH et al (2005) 15-Hydroxyprostaglandin dehydrogenase is down-regulated in colorectal cancer. J Biol Chem 280(5):3217–3223PubMedCrossRef
13.
Zurück zum Zitat Ding Y, Tong M, Liu S, Moscow JA, Tai HH (2005) NAD+-linked 15-hydroxyprostaglandin dehydrogenase (15-PGDH) behaves as a tumor suppressor in lung cancer. Carcinogenesis 26(1):65–72PubMedCrossRef Ding Y, Tong M, Liu S, Moscow JA, Tai HH (2005) NAD+-linked 15-hydroxyprostaglandin dehydrogenase (15-PGDH) behaves as a tumor suppressor in lung cancer. Carcinogenesis 26(1):65–72PubMedCrossRef
14.
Zurück zum Zitat Yan M, Myung SJ, Fink SP, Lawrence E, Lutterbaugh J et al (2009) 15-Hydroxyprostaglandin dehydrogenase inactivation as a mechanism of resistance to celecoxib chemoprevention of colon tumors. Proc Natl Acad Sci U S A 106(23):9409–9413PubMedCrossRef Yan M, Myung SJ, Fink SP, Lawrence E, Lutterbaugh J et al (2009) 15-Hydroxyprostaglandin dehydrogenase inactivation as a mechanism of resistance to celecoxib chemoprevention of colon tumors. Proc Natl Acad Sci U S A 106(23):9409–9413PubMedCrossRef
15.
Zurück zum Zitat Myung SJ, Rerko RM, Yan M, Platzer P, Guda K et al (2006) 15-Hydroxyprostaglandin dehydrogenase is an in vivo suppressor of colon tumorigenesis. Proc Natl Acad Sci U S A 103(32):12098–12102PubMedCrossRef Myung SJ, Rerko RM, Yan M, Platzer P, Guda K et al (2006) 15-Hydroxyprostaglandin dehydrogenase is an in vivo suppressor of colon tumorigenesis. Proc Natl Acad Sci U S A 103(32):12098–12102PubMedCrossRef
16.
Zurück zum Zitat Backlund MG, Mann JR, Holla VR, Shi Q, Daikoku T et al (2008) Repression of 15-hydroxyprostaglandin dehydrogenase involves histone deacetylase 2 and snail in colorectal cancer. Cancer Res 68(22):9331–9337PubMedCrossRef Backlund MG, Mann JR, Holla VR, Shi Q, Daikoku T et al (2008) Repression of 15-hydroxyprostaglandin dehydrogenase involves histone deacetylase 2 and snail in colorectal cancer. Cancer Res 68(22):9331–9337PubMedCrossRef
17.
Zurück zum Zitat Coleman RA, Smith WL, Narumiya S (1994) International Union of Pharmacology classification of prostanoid receptors: properties, distribution, and structure of the receptors and their subtypes. Pharmacol Rev 46(2):205–229PubMed Coleman RA, Smith WL, Narumiya S (1994) International Union of Pharmacology classification of prostanoid receptors: properties, distribution, and structure of the receptors and their subtypes. Pharmacol Rev 46(2):205–229PubMed
18.
19.
Zurück zum Zitat Breyer RM, Bagdassarian CK, Myers SA, Breyer MD (2001) Prostanoid receptors: subtypes and signaling. Annu Rev Pharmacol Toxicol 41:661–690PubMedCrossRef Breyer RM, Bagdassarian CK, Myers SA, Breyer MD (2001) Prostanoid receptors: subtypes and signaling. Annu Rev Pharmacol Toxicol 41:661–690PubMedCrossRef
20.
Zurück zum Zitat Samuelsson B, Morgenstern R, Jakobsson PJ (2007) Membrane prostaglandin E synthase-1: a novel therapeutic target. Pharmacol Rev 59(3):207–224PubMedCrossRef Samuelsson B, Morgenstern R, Jakobsson PJ (2007) Membrane prostaglandin E synthase-1: a novel therapeutic target. Pharmacol Rev 59(3):207–224PubMedCrossRef
21.
Zurück zum Zitat Kalinski P (2012) Regulation of immune responses by prostaglandin e2. J Immunol 188(1):21–28PubMedCrossRef Kalinski P (2012) Regulation of immune responses by prostaglandin e2. J Immunol 188(1):21–28PubMedCrossRef
22.
Zurück zum Zitat Sakata D, Yao C, Narumiya S (2010) Prostaglandin E2, an immunoactivator. J Pharmacol Sci 112(1):1–5PubMedCrossRef Sakata D, Yao C, Narumiya S (2010) Prostaglandin E2, an immunoactivator. J Pharmacol Sci 112(1):1–5PubMedCrossRef
23.
Zurück zum Zitat Wallace JL (2001) Prostaglandin biology in inflammatory bowel disease. Gastroenterol Clin N Am 30(4):971–980CrossRef Wallace JL (2001) Prostaglandin biology in inflammatory bowel disease. Gastroenterol Clin N Am 30(4):971–980CrossRef
24.
Zurück zum Zitat Uematsu S, Matsumoto M, Takeda K, Akira S (2002) Lipopolysaccharide-dependent prostaglandin E(2) production is regulated by the glutathione-dependent prostaglandin E(2) synthase gene induced by the Toll-like receptor 4/MyD88/NF-IL6 pathway. J Immunol 168(11):5811–5816PubMed Uematsu S, Matsumoto M, Takeda K, Akira S (2002) Lipopolysaccharide-dependent prostaglandin E(2) production is regulated by the glutathione-dependent prostaglandin E(2) synthase gene induced by the Toll-like receptor 4/MyD88/NF-IL6 pathway. J Immunol 168(11):5811–5816PubMed
25.
Zurück zum Zitat Hara S, Kamei D, Sasaki Y, Tanemoto A, Nakatani Y et al (2010) Prostaglandin E synthases: understanding their pathophysiological roles through mouse genetic models. Biochimie 92(6):651–659PubMedCrossRef Hara S, Kamei D, Sasaki Y, Tanemoto A, Nakatani Y et al (2010) Prostaglandin E synthases: understanding their pathophysiological roles through mouse genetic models. Biochimie 92(6):651–659PubMedCrossRef
26.
Zurück zum Zitat Kojima F, Kapoor M, Yang L, Fleishaker EL, Ward MR et al (2008) Defective generation of a humoral immune response is associated with a reduced incidence and severity of collagen-induced arthritis in microsomal prostaglandin E synthase-1 null mice. J Immunol 180(12):8361–8368PubMed Kojima F, Kapoor M, Yang L, Fleishaker EL, Ward MR et al (2008) Defective generation of a humoral immune response is associated with a reduced incidence and severity of collagen-induced arthritis in microsomal prostaglandin E synthase-1 null mice. J Immunol 180(12):8361–8368PubMed
27.
Zurück zum Zitat Wang M, Song WL, Cheng Y, Fitzgerald GA (2008) Microsomal prostaglandin E synthase-1 inhibition in cardiovascular inflammatory disease. J Intern Med 263(5):500–505PubMedCrossRef Wang M, Song WL, Cheng Y, Fitzgerald GA (2008) Microsomal prostaglandin E synthase-1 inhibition in cardiovascular inflammatory disease. J Intern Med 263(5):500–505PubMedCrossRef
28.
Zurück zum Zitat Iwakura Y, Ishigame H, Saijo S, Nakae S (2011) Functional specialization of interleukin-17 family members. Immunity 34(2):149–162PubMedCrossRef Iwakura Y, Ishigame H, Saijo S, Nakae S (2011) Functional specialization of interleukin-17 family members. Immunity 34(2):149–162PubMedCrossRef
29.
Zurück zum Zitat Wilson NJ, Boniface K, Chan JR, McKenzie BS, Blumenschein WM et al (2007) Development, cytokine profile and function of human interleukin 17-producing helper T cells. Nat Immunol 8(9):950–957PubMedCrossRef Wilson NJ, Boniface K, Chan JR, McKenzie BS, Blumenschein WM et al (2007) Development, cytokine profile and function of human interleukin 17-producing helper T cells. Nat Immunol 8(9):950–957PubMedCrossRef
30.
Zurück zum Zitat Boniface K, Bak-Jensen KS, Li Y, Blumenschein WM, McGeachy MJ et al (2009) Prostaglandin E2 regulates Th17 cell differentiation and function through cyclic AMP and EP2/EP4 receptor signaling. J Exp Med 206(3):535–548PubMedCrossRef Boniface K, Bak-Jensen KS, Li Y, Blumenschein WM, McGeachy MJ et al (2009) Prostaglandin E2 regulates Th17 cell differentiation and function through cyclic AMP and EP2/EP4 receptor signaling. J Exp Med 206(3):535–548PubMedCrossRef
31.
Zurück zum Zitat Sheibanie AF, Khayrullina T, Safadi FF, Ganea D (2007) Prostaglandin E2 exacerbates collagen-induced arthritis in mice through the inflammatory interleukin-23/interleukin-17 axis. Arthritis Rheum 56(8):2608–2619PubMedCrossRef Sheibanie AF, Khayrullina T, Safadi FF, Ganea D (2007) Prostaglandin E2 exacerbates collagen-induced arthritis in mice through the inflammatory interleukin-23/interleukin-17 axis. Arthritis Rheum 56(8):2608–2619PubMedCrossRef
32.
Zurück zum Zitat Sheibanie AF, Yen JH, Khayrullina T, Emig F, Zhang M et al (2007) The proinflammatory effect of prostaglandin E2 in experimental inflammatory bowel disease is mediated through the IL-23– > IL-17 axis. J Immunol 178(12):8138–8147PubMed Sheibanie AF, Yen JH, Khayrullina T, Emig F, Zhang M et al (2007) The proinflammatory effect of prostaglandin E2 in experimental inflammatory bowel disease is mediated through the IL-23– > IL-17 axis. J Immunol 178(12):8138–8147PubMed
33.
Zurück zum Zitat Fukunaga K, Kohli P, Bonnans C, Fredenburgh LE, Levy BD (2005) Cyclooxygenase 2 plays a pivotal role in the resolution of acute lung injury. J Immunol 174(8):5033–5039PubMed Fukunaga K, Kohli P, Bonnans C, Fredenburgh LE, Levy BD (2005) Cyclooxygenase 2 plays a pivotal role in the resolution of acute lung injury. J Immunol 174(8):5033–5039PubMed
34.
Zurück zum Zitat Gilroy DW, Colville-Nash PR, Willis D, Chivers J, Paul-Clark MJ et al (1999) Inducible cyclooxygenase may have anti-inflammatory properties. Nat Med 5(6):698–701PubMedCrossRef Gilroy DW, Colville-Nash PR, Willis D, Chivers J, Paul-Clark MJ et al (1999) Inducible cyclooxygenase may have anti-inflammatory properties. Nat Med 5(6):698–701PubMedCrossRef
35.
Zurück zum Zitat Wallace JL (2006) COX-2: a pivotal enzyme in mucosal protection and resolution of inflammation. Sci World J 6:577–588CrossRef Wallace JL (2006) COX-2: a pivotal enzyme in mucosal protection and resolution of inflammation. Sci World J 6:577–588CrossRef
36.
Zurück zum Zitat Yin H, Cheng L, Langenbach R, Ju C (2007) Prostaglandin I(2) and E(2) mediate the protective effects of cyclooxygenase-2 in a mouse model of immune-mediated liver injury. Hepatology 45(1):159–169PubMedCrossRef Yin H, Cheng L, Langenbach R, Ju C (2007) Prostaglandin I(2) and E(2) mediate the protective effects of cyclooxygenase-2 in a mouse model of immune-mediated liver injury. Hepatology 45(1):159–169PubMedCrossRef
37.
Zurück zum Zitat Scher JU, Pillinger MH (2009) The anti-inflammatory effects of prostaglandins. J Investig Med 57(6):703–708PubMed Scher JU, Pillinger MH (2009) The anti-inflammatory effects of prostaglandins. J Investig Med 57(6):703–708PubMed
38.
Zurück zum Zitat Joshi PC, Zhou X, Cuchens M, Jones Q (2001) Prostaglandin E2 suppressed IL-15-mediated human NK cell function through down-regulation of common gamma-chain. J Immunol 166(2):885–891PubMed Joshi PC, Zhou X, Cuchens M, Jones Q (2001) Prostaglandin E2 suppressed IL-15-mediated human NK cell function through down-regulation of common gamma-chain. J Immunol 166(2):885–891PubMed
39.
Zurück zum Zitat Linnemeyer PA, Pollack SB (1993) Prostaglandin E2-induced changes in the phenotype, morphology, and lytic activity of IL-2-activated natural killer cells. J Immunol 150(9):3747–3754PubMed Linnemeyer PA, Pollack SB (1993) Prostaglandin E2-induced changes in the phenotype, morphology, and lytic activity of IL-2-activated natural killer cells. J Immunol 150(9):3747–3754PubMed
40.
Zurück zum Zitat Martinet L, Jean C, Dietrich G, Fournie JJ, Poupot R (2010) PGE2 inhibits natural killer and gamma delta T cell cytotoxicity triggered by NKR and TCR through a cAMP-mediated PKA type I-dependent signaling. Biochem Pharmacol 80(6):838–845PubMedCrossRef Martinet L, Jean C, Dietrich G, Fournie JJ, Poupot R (2010) PGE2 inhibits natural killer and gamma delta T cell cytotoxicity triggered by NKR and TCR through a cAMP-mediated PKA type I-dependent signaling. Biochem Pharmacol 80(6):838–845PubMedCrossRef
41.
Zurück zum Zitat Yakar I, Melamed R, Shakhar G, Shakhar K, Rosenne E et al (2003) Prostaglandin e(2) suppresses NK activity in vivo and promotes postoperative tumor metastasis in rats. Ann Surg Oncol 10(4):469–479PubMedCrossRef Yakar I, Melamed R, Shakhar G, Shakhar K, Rosenne E et al (2003) Prostaglandin e(2) suppresses NK activity in vivo and promotes postoperative tumor metastasis in rats. Ann Surg Oncol 10(4):469–479PubMedCrossRef
42.
Zurück zum Zitat Muthuswamy R, Mueller-Berghaus J, Haberkorn U, Reinhart TA, Schadendorf D et al (2010) PGE(2) transiently enhances DC expression of CCR7 but inhibits the ability of DCs to produce CCL19 and attract naive T cells. Blood 116(9):1454–1459PubMedCrossRef Muthuswamy R, Mueller-Berghaus J, Haberkorn U, Reinhart TA, Schadendorf D et al (2010) PGE(2) transiently enhances DC expression of CCR7 but inhibits the ability of DCs to produce CCL19 and attract naive T cells. Blood 116(9):1454–1459PubMedCrossRef
43.
Zurück zum Zitat Betz M, Fox BS (1991) Prostaglandin E2 inhibits production of Th1 lymphokines but not of Th2 lymphokines. J Immunol 146(1):108–113PubMed Betz M, Fox BS (1991) Prostaglandin E2 inhibits production of Th1 lymphokines but not of Th2 lymphokines. J Immunol 146(1):108–113PubMed
44.
Zurück zum Zitat Snijdewint FG, Kalinski P, Wierenga EA, Bos JD, Kapsenberg ML (1993) Prostaglandin E2 differentially modulates cytokine secretion profiles of human T helper lymphocytes. J Immunol 150(12):5321–5329PubMed Snijdewint FG, Kalinski P, Wierenga EA, Bos JD, Kapsenberg ML (1993) Prostaglandin E2 differentially modulates cytokine secretion profiles of human T helper lymphocytes. J Immunol 150(12):5321–5329PubMed
45.
Zurück zum Zitat Allen JE, Wynn TA (2011) Evolution of Th2 immunity: a rapid repair response to tissue destructive pathogens. PLoS Pathog 7(5):e1002003PubMedCrossRef Allen JE, Wynn TA (2011) Evolution of Th2 immunity: a rapid repair response to tissue destructive pathogens. PLoS Pathog 7(5):e1002003PubMedCrossRef
46.
Zurück zum Zitat Ae T, Ohno T, Hattori Y, Suzuki T, Hosono K et al (2010) Role of microsomal prostaglandin E synthase-1 in the facilitation of angiogenesis and the healing of gastric ulcers. Am J Physiol Gastrointest Liver Physiol 299(5):G1139–G1146PubMedCrossRef Ae T, Ohno T, Hattori Y, Suzuki T, Hosono K et al (2010) Role of microsomal prostaglandin E synthase-1 in the facilitation of angiogenesis and the healing of gastric ulcers. Am J Physiol Gastrointest Liver Physiol 299(5):G1139–G1146PubMedCrossRef
47.
Zurück zum Zitat Kabashima K, Saji T, Murata T, Nagamachi M, Matsuoka T et al (2002) The prostaglandin receptor EP4 suppresses colitis, mucosal damage and CD4 cell activation in the gut. J Clin Invest 109(7):883–893PubMed Kabashima K, Saji T, Murata T, Nagamachi M, Matsuoka T et al (2002) The prostaglandin receptor EP4 suppresses colitis, mucosal damage and CD4 cell activation in the gut. J Clin Invest 109(7):883–893PubMed
48.
Zurück zum Zitat Nakanishi M, Menoret A, Tanaka T, Miyamoto S, Montrose DC et al (2011) Selective PGE(2) suppression inhibits colon carcinogenesis and modifies local mucosal immunity. Cancer Prev Res (Phila) 4(8):1198–1208CrossRef Nakanishi M, Menoret A, Tanaka T, Miyamoto S, Montrose DC et al (2011) Selective PGE(2) suppression inhibits colon carcinogenesis and modifies local mucosal immunity. Cancer Prev Res (Phila) 4(8):1198–1208CrossRef
49.
Zurück zum Zitat Gurtner GC, Werner S, Barrandon Y, Longaker MT (2008) Wound repair and regeneration. Nature 453(7193):314–321PubMedCrossRef Gurtner GC, Werner S, Barrandon Y, Longaker MT (2008) Wound repair and regeneration. Nature 453(7193):314–321PubMedCrossRef
50.
Zurück zum Zitat Montrose DC, Kadaveru K, Ilsley JN, Root SH, Rajan TV et al (2010) cPLA2 is protective against COX inhibitor-induced intestinal damage. Toxicol Sci 117(1):122–132PubMedCrossRef Montrose DC, Kadaveru K, Ilsley JN, Root SH, Rajan TV et al (2010) cPLA2 is protective against COX inhibitor-induced intestinal damage. Toxicol Sci 117(1):122–132PubMedCrossRef
51.
Zurück zum Zitat Iizuka M, Konno S (2011) Wound healing of intestinal epithelial cells. World J Gastroenterol: WJG 17(17):2161–2171PubMedCrossRef Iizuka M, Konno S (2011) Wound healing of intestinal epithelial cells. World J Gastroenterol: WJG 17(17):2161–2171PubMedCrossRef
52.
Zurück zum Zitat Castellone MD, Teramoto H, Williams BO, Druey KM, Gutkind JS (2005) Prostaglandin E2 promotes colon cancer cell growth through a Gs-axin-beta-catenin signaling axis. Science 310(5753):1504–1510PubMedCrossRef Castellone MD, Teramoto H, Williams BO, Druey KM, Gutkind JS (2005) Prostaglandin E2 promotes colon cancer cell growth through a Gs-axin-beta-catenin signaling axis. Science 310(5753):1504–1510PubMedCrossRef
53.
Zurück zum Zitat Buchanan FG, Wang D, Bargiacchi F, DuBois RN (2003) Prostaglandin E2 regulates cell migration via the intracellular activation of the epidermal growth factor receptor. J Biol Chem 278(37):35451–35457PubMedCrossRef Buchanan FG, Wang D, Bargiacchi F, DuBois RN (2003) Prostaglandin E2 regulates cell migration via the intracellular activation of the epidermal growth factor receptor. J Biol Chem 278(37):35451–35457PubMedCrossRef
54.
Zurück zum Zitat Nakanishi M, Sato T, Li Y, Nelson AJ, Farid M et al (2012) Prostaglandin E2 stimulates the production of vascular endothelial growth factor through the E-prostanoid-2 receptor in cultured human lung fibroblasts. Am J Respir Cell Mol Biol 46(2):217–223PubMedCrossRef Nakanishi M, Sato T, Li Y, Nelson AJ, Farid M et al (2012) Prostaglandin E2 stimulates the production of vascular endothelial growth factor through the E-prostanoid-2 receptor in cultured human lung fibroblasts. Am J Respir Cell Mol Biol 46(2):217–223PubMedCrossRef
55.
Zurück zum Zitat Guo X, Oshima H, Kitmura T, Taketo MM, Oshima M (2008) Stromal fibroblasts activated by tumor cells promote angiogenesis in mouse gastric cancer. J Biol Chem 283(28):19864–19871PubMedCrossRef Guo X, Oshima H, Kitmura T, Taketo MM, Oshima M (2008) Stromal fibroblasts activated by tumor cells promote angiogenesis in mouse gastric cancer. J Biol Chem 283(28):19864–19871PubMedCrossRef
56.
Zurück zum Zitat Zhang Y, Daaka Y (2011) PGE2 promotes angiogenesis through EP4 and PKA Cgamma pathway. Blood 118(19):5355–5364PubMedCrossRef Zhang Y, Daaka Y (2011) PGE2 promotes angiogenesis through EP4 and PKA Cgamma pathway. Blood 118(19):5355–5364PubMedCrossRef
57.
Zurück zum Zitat Zhu Z, Fu C, Li X, Song Y, Li C et al (2011) Prostaglandin E2 promotes endothelial differentiation from bone marrow-derived cells through AMPK activation. PLoS One 6(8):e23554PubMedCrossRef Zhu Z, Fu C, Li X, Song Y, Li C et al (2011) Prostaglandin E2 promotes endothelial differentiation from bone marrow-derived cells through AMPK activation. PLoS One 6(8):e23554PubMedCrossRef
58.
Zurück zum Zitat Rao R, Redha R, Macias-Perez I, Su Y, Hao C et al (2007) Prostaglandin E2-EP4 receptor promotes endothelial cell migration via ERK activation and angiogenesis in vivo. J Biol Chem 282(23):16959–16968PubMedCrossRef Rao R, Redha R, Macias-Perez I, Su Y, Hao C et al (2007) Prostaglandin E2-EP4 receptor promotes endothelial cell migration via ERK activation and angiogenesis in vivo. J Biol Chem 282(23):16959–16968PubMedCrossRef
59.
Zurück zum Zitat Sipos F, Valcz G, Molnar B (2012) Physiological and pathological role of local and immigrating colonic stem cells. World J Gastroenterol: WJG 18(4):295–301PubMedCrossRef Sipos F, Valcz G, Molnar B (2012) Physiological and pathological role of local and immigrating colonic stem cells. World J Gastroenterol: WJG 18(4):295–301PubMedCrossRef
60.
Zurück zum Zitat Kolodsick JE, Peters-Golden M, Larios J, Toews GB, Thannickal VJ et al (2003) Prostaglandin E2 inhibits fibroblast to myofibroblast transition via E. prostanoid receptor 2 signaling and cyclic adenosine monophosphate elevation. Am J Respir Cell Mol Biol 29(5):537–544PubMedCrossRef Kolodsick JE, Peters-Golden M, Larios J, Toews GB, Thannickal VJ et al (2003) Prostaglandin E2 inhibits fibroblast to myofibroblast transition via E. prostanoid receptor 2 signaling and cyclic adenosine monophosphate elevation. Am J Respir Cell Mol Biol 29(5):537–544PubMedCrossRef
61.
Zurück zum Zitat Walker NM, Badri LN, Wadhwa A, Wettlaufer S, Peters-Golden M et al (2012) Prostaglandin E2 as an inhibitory modulator of fibrogenesis in human lung allografts. Am J Respir Crit Care Med 185(1):77–84PubMedCrossRef Walker NM, Badri LN, Wadhwa A, Wettlaufer S, Peters-Golden M et al (2012) Prostaglandin E2 as an inhibitory modulator of fibrogenesis in human lung allografts. Am J Respir Crit Care Med 185(1):77–84PubMedCrossRef
62.
Zurück zum Zitat McCann MR, Monemdjou R, Ghassemi-Kakroodi P, Fahmi H, Perez G et al (2011) mPGES-1 null mice are resistant to bleomycin-induced skin fibrosis. Arthritis Res Ther 13(1):R6PubMedCrossRef McCann MR, Monemdjou R, Ghassemi-Kakroodi P, Fahmi H, Perez G et al (2011) mPGES-1 null mice are resistant to bleomycin-induced skin fibrosis. Arthritis Res Ther 13(1):R6PubMedCrossRef
63.
Zurück zum Zitat Iwanaga K, Okada M, Murata T, Hori M, Ozaki H (2012) Prostaglandin E2 promotes wound-induced migration of intestinal subepithelial myofibroblasts via EP2, EP3, and EP4 prostanoid receptor activation. J Pharmacol Exp Ther 340(3):604–611PubMedCrossRef Iwanaga K, Okada M, Murata T, Hori M, Ozaki H (2012) Prostaglandin E2 promotes wound-induced migration of intestinal subepithelial myofibroblasts via EP2, EP3, and EP4 prostanoid receptor activation. J Pharmacol Exp Ther 340(3):604–611PubMedCrossRef
64.
Zurück zum Zitat Harding P, LaPointe MC (2011) Prostaglandin E2 increases cardiac fibroblast proliferation and increases cyclin D expression via EP1 receptor. Prostaglandins Leukot Essent Fat Acids 84(5–6):147–152CrossRef Harding P, LaPointe MC (2011) Prostaglandin E2 increases cardiac fibroblast proliferation and increases cyclin D expression via EP1 receptor. Prostaglandins Leukot Essent Fat Acids 84(5–6):147–152CrossRef
65.
Zurück zum Zitat Ayabe S, Murata T, Maruyama T, Hori M, Ozaki H (2009) Prostaglandin E2 induces contraction of liver myofibroblasts by activating EP3 and FP prostanoid receptors. Br J Pharmacol 156(5):835–845PubMedCrossRef Ayabe S, Murata T, Maruyama T, Hori M, Ozaki H (2009) Prostaglandin E2 induces contraction of liver myofibroblasts by activating EP3 and FP prostanoid receptors. Br J Pharmacol 156(5):835–845PubMedCrossRef
66.
Zurück zum Zitat Fischer SM, Hawk ET, Lubet RA (2011) Coxibs and other nonsteroidal anti-inflammatory drugs in animal models of cancer chemoprevention. Cancer Prev Res 4(11):1728–1735CrossRef Fischer SM, Hawk ET, Lubet RA (2011) Coxibs and other nonsteroidal anti-inflammatory drugs in animal models of cancer chemoprevention. Cancer Prev Res 4(11):1728–1735CrossRef
67.
Zurück zum Zitat Waddell WR, Ganser GF, Cerise EJ, Loughry RW (1989) Sulindac for polyposis of the colon. Am J Surg 157(1):175–179PubMedCrossRef Waddell WR, Ganser GF, Cerise EJ, Loughry RW (1989) Sulindac for polyposis of the colon. Am J Surg 157(1):175–179PubMedCrossRef
68.
Zurück zum Zitat Waddell WR, Loughry RW (1983) Sulindac for polyposis of the colon. J Surg Oncol 24(1):83–87PubMedCrossRef Waddell WR, Loughry RW (1983) Sulindac for polyposis of the colon. J Surg Oncol 24(1):83–87PubMedCrossRef
69.
Zurück zum Zitat Rosenberg L, Palmer JR, Zauber AG, Warshauer ME, Stolley PD et al (1991) A hypothesis: nonsteroidal anti-inflammatory drugs reduce the incidence of large-bowel cancer. J Natl Cancer Inst 83(5):355–358PubMedCrossRef Rosenberg L, Palmer JR, Zauber AG, Warshauer ME, Stolley PD et al (1991) A hypothesis: nonsteroidal anti-inflammatory drugs reduce the incidence of large-bowel cancer. J Natl Cancer Inst 83(5):355–358PubMedCrossRef
70.
Zurück zum Zitat Thun MJ, Namboodiri MM, Heath CW Jr (1991) Aspirin use and reduced risk of fatal colon cancer. N Engl J Med 325(23):1593–1596PubMedCrossRef Thun MJ, Namboodiri MM, Heath CW Jr (1991) Aspirin use and reduced risk of fatal colon cancer. N Engl J Med 325(23):1593–1596PubMedCrossRef
71.
Zurück zum Zitat Kawamori T, Uchiya N, Sugimura T, Wakabayashi K (2003) Enhancement of colon carcinogenesis by prostaglandin E2 administration. Carcinogenesis 24(5):985–990PubMedCrossRef Kawamori T, Uchiya N, Sugimura T, Wakabayashi K (2003) Enhancement of colon carcinogenesis by prostaglandin E2 administration. Carcinogenesis 24(5):985–990PubMedCrossRef
72.
Zurück zum Zitat Wang D, Buchanan FG, Wang H, Dey SK, DuBois RN (2005) Prostaglandin E2 enhances intestinal adenoma growth via activation of the Ras-mitogen-activated protein kinase cascade. Cancer Res 65(5):1822–1829PubMedCrossRef Wang D, Buchanan FG, Wang H, Dey SK, DuBois RN (2005) Prostaglandin E2 enhances intestinal adenoma growth via activation of the Ras-mitogen-activated protein kinase cascade. Cancer Res 65(5):1822–1829PubMedCrossRef
73.
Zurück zum Zitat Wilson JW, Potten CS (2000) The effect of exogenous prostaglandin administration on tumor size and yield in Min/+ mice. Cancer Res 60(16):4645–4653PubMed Wilson JW, Potten CS (2000) The effect of exogenous prostaglandin administration on tumor size and yield in Min/+ mice. Cancer Res 60(16):4645–4653PubMed
74.
Zurück zum Zitat Nakanishi M, Montrose DC, Clark P, Nambiar PR, Belinsky GS et al (2008) Genetic deletion of mPGES-1 suppresses intestinal tumorigenesis. Cancer Res 68(9):3251–3259PubMedCrossRef Nakanishi M, Montrose DC, Clark P, Nambiar PR, Belinsky GS et al (2008) Genetic deletion of mPGES-1 suppresses intestinal tumorigenesis. Cancer Res 68(9):3251–3259PubMedCrossRef
75.
Zurück zum Zitat Cianchi F, Cortesini C, Bechi P, Fantappie O, Messerini L et al (2001) Up-regulation of cyclooxygenase 2 gene expression correlates with tumor angiogenesis in human colorectal cancer. Gastroenterology 121(6):1339–1347PubMedCrossRef Cianchi F, Cortesini C, Bechi P, Fantappie O, Messerini L et al (2001) Up-regulation of cyclooxygenase 2 gene expression correlates with tumor angiogenesis in human colorectal cancer. Gastroenterology 121(6):1339–1347PubMedCrossRef
76.
Zurück zum Zitat Guda K, Upender MB, Belinsky G, Flynn C, Nakanishi M et al (2004) Carcinogen-induced colon tumors in mice are chromosomally stable and are characterized by low-level microsatellite instability. Oncogene 23(21):3813–3821PubMedCrossRef Guda K, Upender MB, Belinsky G, Flynn C, Nakanishi M et al (2004) Carcinogen-induced colon tumors in mice are chromosomally stable and are characterized by low-level microsatellite instability. Oncogene 23(21):3813–3821PubMedCrossRef
77.
Zurück zum Zitat Nambiar PR, Nakanishi M, Gupta R, Cheung E, Firouzi A et al (2004) Genetic signatures of high- and low-risk aberrant crypt foci in a mouse model of sporadic colon cancer. Cancer Res 64(18):6394–6401PubMedCrossRef Nambiar PR, Nakanishi M, Gupta R, Cheung E, Firouzi A et al (2004) Genetic signatures of high- and low-risk aberrant crypt foci in a mouse model of sporadic colon cancer. Cancer Res 64(18):6394–6401PubMedCrossRef
78.
Zurück zum Zitat Papanikolaou A, Wang QS, Papanikolaou D, Whiteley HE, Rosenberg DW (2000) Sequential and morphological analyses of aberrant crypt foci formation in mice of differing susceptibility to azoxymethane-induced colon carcinogenesis. Carcinogenesis 21(8):1567–1572PubMedCrossRef Papanikolaou A, Wang QS, Papanikolaou D, Whiteley HE, Rosenberg DW (2000) Sequential and morphological analyses of aberrant crypt foci formation in mice of differing susceptibility to azoxymethane-induced colon carcinogenesis. Carcinogenesis 21(8):1567–1572PubMedCrossRef
79.
Zurück zum Zitat Chen EP, Smyth EM (2011) COX-2 and PGE2-dependent immunomodulation in breast cancer. Prostaglandins Other Lipid Mediat 96(1–4):14–20PubMedCrossRef Chen EP, Smyth EM (2011) COX-2 and PGE2-dependent immunomodulation in breast cancer. Prostaglandins Other Lipid Mediat 96(1–4):14–20PubMedCrossRef
80.
Zurück zum Zitat Markosyan N, Chen EP, Ndong VN, Yao Y, Sterner CJ et al (2011) Deletion of cyclooxygenase 2 in mouse mammary epithelial cells delays breast cancer onset through augmentation of type 1 immune responses in tumors. Carcinogenesis 32(10):1441–1449PubMedCrossRef Markosyan N, Chen EP, Ndong VN, Yao Y, Sterner CJ et al (2011) Deletion of cyclooxygenase 2 in mouse mammary epithelial cells delays breast cancer onset through augmentation of type 1 immune responses in tumors. Carcinogenesis 32(10):1441–1449PubMedCrossRef
81.
Zurück zum Zitat Oshima H, Oshima M, Inaba K, Taketo MM (2004) Hyperplastic gastric tumors induced by activated macrophages in COX-2/mPGES-1 transgenic mice. EMBO J 23(7):1669–1678PubMedCrossRef Oshima H, Oshima M, Inaba K, Taketo MM (2004) Hyperplastic gastric tumors induced by activated macrophages in COX-2/mPGES-1 transgenic mice. EMBO J 23(7):1669–1678PubMedCrossRef
82.
Zurück zum Zitat Itadani H, Oshima H, Oshima M, Kotani H (2009) Mouse gastric tumor models with prostaglandin E2 pathway activation show similar gene expression profiles to intestinal-type human gastric cancer. BMC Genomics 10:615PubMedCrossRef Itadani H, Oshima H, Oshima M, Kotani H (2009) Mouse gastric tumor models with prostaglandin E2 pathway activation show similar gene expression profiles to intestinal-type human gastric cancer. BMC Genomics 10:615PubMedCrossRef
83.
Zurück zum Zitat Oshima H, Matsunaga A, Fujimura T, Tsukamoto T, Taketo MM et al (2006) Carcinogenesis in mouse stomach by simultaneous activation of the Wnt signaling and prostaglandin E2 pathway. Gastroenterology 131(4):1086–1095PubMedCrossRef Oshima H, Matsunaga A, Fujimura T, Tsukamoto T, Taketo MM et al (2006) Carcinogenesis in mouse stomach by simultaneous activation of the Wnt signaling and prostaglandin E2 pathway. Gastroenterology 131(4):1086–1095PubMedCrossRef
84.
Zurück zum Zitat Oshima H, Oguma K, Du YC, Oshima M (2009) Prostaglandin E2, Wnt, and BMP in gastric tumor mouse models. Cancer Sci 100(10):1779–1785PubMedCrossRef Oshima H, Oguma K, Du YC, Oshima M (2009) Prostaglandin E2, Wnt, and BMP in gastric tumor mouse models. Cancer Sci 100(10):1779–1785PubMedCrossRef
85.
Zurück zum Zitat Mutoh M, Watanabe K, Kitamura T, Shoji Y, Takahashi M et al (2002) Involvement of prostaglandin E receptor subtype EP(4) in colon carcinogenesis. Cancer Res 62(1):28–32PubMed Mutoh M, Watanabe K, Kitamura T, Shoji Y, Takahashi M et al (2002) Involvement of prostaglandin E receptor subtype EP(4) in colon carcinogenesis. Cancer Res 62(1):28–32PubMed
86.
Zurück zum Zitat Chell SD, Witherden IR, Dobson RR, Moorghen M, Herman AA et al (2006) Increased EP4 receptor expression in colorectal cancer progression promotes cell growth and anchorage independence. Cancer Res 66(6):3106–3113PubMedCrossRef Chell SD, Witherden IR, Dobson RR, Moorghen M, Herman AA et al (2006) Increased EP4 receptor expression in colorectal cancer progression promotes cell growth and anchorage independence. Cancer Res 66(6):3106–3113PubMedCrossRef
87.
Zurück zum Zitat Doherty GA, Byrne SM, Molloy ES, Malhotra V, Austin SC et al (2009) Proneoplastic effects of PGE2 mediated by EP4 receptor in colorectal cancer. BMC Cancer 9:207PubMedCrossRef Doherty GA, Byrne SM, Molloy ES, Malhotra V, Austin SC et al (2009) Proneoplastic effects of PGE2 mediated by EP4 receptor in colorectal cancer. BMC Cancer 9:207PubMedCrossRef
88.
Zurück zum Zitat Chandramouli A, Onyeagucha BC, Mercado-Pimentel ME, Stankova L, Shahin NA et al (2012) MicroRNA-101 (miR-101) post-transcriptionally regulates the expression of EP4 receptor in colon cancers. Cancer Biol Ther 13(3):175–183PubMedCrossRef Chandramouli A, Onyeagucha BC, Mercado-Pimentel ME, Stankova L, Shahin NA et al (2012) MicroRNA-101 (miR-101) post-transcriptionally regulates the expression of EP4 receptor in colon cancers. Cancer Biol Ther 13(3):175–183PubMedCrossRef
89.
Zurück zum Zitat Watanabe K, Kawamori T, Nakatsugi S, Ohta T, Ohuchida S et al (1999) Role of the prostaglandin E receptor subtype EP1 in colon carcinogenesis. Cancer Res 59(20):5093–5096PubMed Watanabe K, Kawamori T, Nakatsugi S, Ohta T, Ohuchida S et al (1999) Role of the prostaglandin E receptor subtype EP1 in colon carcinogenesis. Cancer Res 59(20):5093–5096PubMed
90.
Zurück zum Zitat Shoji Y, Takahashi M, Kitamura T, Watanabe K, Kawamori T et al (2004) Downregulation of prostaglandin E receptor subtype EP3 during colon cancer development. Gut 53(8):1151–1158PubMedCrossRef Shoji Y, Takahashi M, Kitamura T, Watanabe K, Kawamori T et al (2004) Downregulation of prostaglandin E receptor subtype EP3 during colon cancer development. Gut 53(8):1151–1158PubMedCrossRef
91.
Zurück zum Zitat Xia D, Wang D, Kim SH, Katoh H, DuBois RN (2012) Prostaglandin E2 promotes intestinal tumor growth via DNA methylation. Nat Med 18(2):224–226PubMedCrossRef Xia D, Wang D, Kim SH, Katoh H, DuBois RN (2012) Prostaglandin E2 promotes intestinal tumor growth via DNA methylation. Nat Med 18(2):224–226PubMedCrossRef
92.
Zurück zum Zitat Sonoshita M, Takaku K, Sasaki N, Sugimoto Y, Ushikubi F et al (2001) Acceleration of intestinal polyposis through prostaglandin receptor EP2 in Apc(Delta 716) knockout mice. Nat Med 7(9):1048–1051PubMedCrossRef Sonoshita M, Takaku K, Sasaki N, Sugimoto Y, Ushikubi F et al (2001) Acceleration of intestinal polyposis through prostaglandin receptor EP2 in Apc(Delta 716) knockout mice. Nat Med 7(9):1048–1051PubMedCrossRef
93.
Zurück zum Zitat Jimenez P, Piazuelo E, Cebrian C, Ortego J, Strunk M et al (2010) Prostaglandin EP2 receptor expression is increased in Barrett's oesophagus and oesophageal adenocarcinoma. Aliment Pharmacol Ther 31(3):440–451PubMedCrossRef Jimenez P, Piazuelo E, Cebrian C, Ortego J, Strunk M et al (2010) Prostaglandin EP2 receptor expression is increased in Barrett's oesophagus and oesophageal adenocarcinoma. Aliment Pharmacol Ther 31(3):440–451PubMedCrossRef
94.
Zurück zum Zitat Jin J, Chang Y, Wei W, He YF, Hu SS et al (2012) Prostanoid EP1 receptor as the target of (−)-epigallocatechin-3-gallate in suppressing hepatocellular carcinoma cells in vitro. Acta Pharmacol Sin 33(5):701–709PubMedCrossRef Jin J, Chang Y, Wei W, He YF, Hu SS et al (2012) Prostanoid EP1 receptor as the target of (−)-epigallocatechin-3-gallate in suppressing hepatocellular carcinoma cells in vitro. Acta Pharmacol Sin 33(5):701–709PubMedCrossRef
95.
Zurück zum Zitat Amano H, Ito Y, Suzuki T, Kato S, Matsui Y et al (2009) Roles of a prostaglandin E-type receptor, EP3, in upregulation of matrix metalloproteinase-9 and vascular endothelial growth factor during enhancement of tumor metastasis. Cancer Sci 100(12):2318–2324PubMedCrossRef Amano H, Ito Y, Suzuki T, Kato S, Matsui Y et al (2009) Roles of a prostaglandin E-type receptor, EP3, in upregulation of matrix metalloproteinase-9 and vascular endothelial growth factor during enhancement of tumor metastasis. Cancer Sci 100(12):2318–2324PubMedCrossRef
96.
97.
Zurück zum Zitat Holt DM, Ma X, Kundu N, Collin PD, Fulton AM (2012) Modulation of host natural killer cell functions in breast cancer via prostaglandin E2 receptors EP2 and EP4. J Immunother 35(2):179–188PubMedCrossRef Holt DM, Ma X, Kundu N, Collin PD, Fulton AM (2012) Modulation of host natural killer cell functions in breast cancer via prostaglandin E2 receptors EP2 and EP4. J Immunother 35(2):179–188PubMedCrossRef
98.
Zurück zum Zitat Liu L, Ge D, Ma L, Mei J, Liu S et al (2012) Interleukin-17 and prostaglandin E2 are involved in formation of an M2 macrophage-dominant microenvironment in lung cancer. J Thorac Oncol 7(7):1091–1100PubMedCrossRef Liu L, Ge D, Ma L, Mei J, Liu S et al (2012) Interleukin-17 and prostaglandin E2 are involved in formation of an M2 macrophage-dominant microenvironment in lung cancer. J Thorac Oncol 7(7):1091–1100PubMedCrossRef
99.
Zurück zum Zitat Betts GJ, Clarke SL, Richards HE, Godkin AJ, Gallimore AM (2006) Regulating the immune response to tumours. Adv Drug Deliv Rev 58(8):948–961PubMedCrossRef Betts GJ, Clarke SL, Richards HE, Godkin AJ, Gallimore AM (2006) Regulating the immune response to tumours. Adv Drug Deliv Rev 58(8):948–961PubMedCrossRef
100.
Zurück zum Zitat Ostrand-Rosenberg S, Sinha P (2009) Myeloid-derived suppressor cells: linking inflammation and cancer. J Immunol 182(8):4499–4506PubMedCrossRef Ostrand-Rosenberg S, Sinha P (2009) Myeloid-derived suppressor cells: linking inflammation and cancer. J Immunol 182(8):4499–4506PubMedCrossRef
101.
Zurück zum Zitat Izcue A, Coombes JL, Powrie F (2009) Regulatory lymphocytes and intestinal inflammation. Annu Rev Immunol 27:313–338PubMedCrossRef Izcue A, Coombes JL, Powrie F (2009) Regulatory lymphocytes and intestinal inflammation. Annu Rev Immunol 27:313–338PubMedCrossRef
102.
Zurück zum Zitat Fehervari Z, Sakaguchi S (2004) CD4+ Tregs and immune control. J Clin Investig 114(9):1209–1217PubMed Fehervari Z, Sakaguchi S (2004) CD4+ Tregs and immune control. J Clin Investig 114(9):1209–1217PubMed
103.
Zurück zum Zitat Baratelli F, Lin Y, Zhu L, Yang SC, Heuze-Vourc'h N et al (2005) Prostaglandin E2 induces FOXP3 gene expression and T regulatory cell function in human CD4+ T cells. J Immunol 175(3):1483–1490PubMed Baratelli F, Lin Y, Zhu L, Yang SC, Heuze-Vourc'h N et al (2005) Prostaglandin E2 induces FOXP3 gene expression and T regulatory cell function in human CD4+ T cells. J Immunol 175(3):1483–1490PubMed
104.
Zurück zum Zitat Sharma S, Yang SC, Zhu L, Reckamp K, Gardner B et al (2005) Tumor cyclooxygenase-2/prostaglandin E2-dependent promotion of FOXP3 expression and CD4+ CD25+ T regulatory cell activities in lung cancer. Cancer Res 65(12):5211–5220PubMedCrossRef Sharma S, Yang SC, Zhu L, Reckamp K, Gardner B et al (2005) Tumor cyclooxygenase-2/prostaglandin E2-dependent promotion of FOXP3 expression and CD4+ CD25+ T regulatory cell activities in lung cancer. Cancer Res 65(12):5211–5220PubMedCrossRef
105.
Zurück zum Zitat Yuan XL, Chen L, Li MX, Dong P, Xue J et al (2010) Elevated expression of Foxp3 in tumor-infiltrating Treg cells suppresses T-cell proliferation and contributes to gastric cancer progression in a COX-2-dependent manner. Clin Immunol 134(3):277–288PubMedCrossRef Yuan XL, Chen L, Li MX, Dong P, Xue J et al (2010) Elevated expression of Foxp3 in tumor-infiltrating Treg cells suppresses T-cell proliferation and contributes to gastric cancer progression in a COX-2-dependent manner. Clin Immunol 134(3):277–288PubMedCrossRef
106.
Zurück zum Zitat Yokokawa J, Cereda V, Remondo C, Gulley JL, Arlen PM et al (2008) Enhanced functionality of CD4 + CD25(high)FoxP3+ regulatory T cells in the peripheral blood of patients with prostate cancer. Clin Cancer Res Off J Am Assoc Cancer Res 14(4):1032–1040CrossRef Yokokawa J, Cereda V, Remondo C, Gulley JL, Arlen PM et al (2008) Enhanced functionality of CD4 + CD25(high)FoxP3+ regulatory T cells in the peripheral blood of patients with prostate cancer. Clin Cancer Res Off J Am Assoc Cancer Res 14(4):1032–1040CrossRef
107.
Zurück zum Zitat Lee SY, Choi HK, Lee KJ, Jung JY, Hur GY et al (2009) The immune tolerance of cancer is mediated by IDO that is inhibited by COX-2 inhibitors through regulatory T cells. J Immunother 32(1):22–28PubMedCrossRef Lee SY, Choi HK, Lee KJ, Jung JY, Hur GY et al (2009) The immune tolerance of cancer is mediated by IDO that is inhibited by COX-2 inhibitors through regulatory T cells. J Immunother 32(1):22–28PubMedCrossRef
108.
Zurück zum Zitat Mandapathil M, Szczepanski MJ, Szajnik M, Ren J, Jackson EK et al (2010) Adenosine and prostaglandin E2 cooperate in the suppression of immune responses mediated by adaptive regulatory T cells. J Biol Chem 285(36):27571–27580PubMedCrossRef Mandapathil M, Szczepanski MJ, Szajnik M, Ren J, Jackson EK et al (2010) Adenosine and prostaglandin E2 cooperate in the suppression of immune responses mediated by adaptive regulatory T cells. J Biol Chem 285(36):27571–27580PubMedCrossRef
109.
Zurück zum Zitat Soontrapa K, Honda T, Sakata D, Yao C, Hirata T et al (2011) Prostaglandin E2-prostaglandin E receptor subtype 4 (EP4) signaling mediates UV irradiation-induced systemic immunosuppression. Proc Natl Acad Sci U S A 108(16):6668–6673PubMedCrossRef Soontrapa K, Honda T, Sakata D, Yao C, Hirata T et al (2011) Prostaglandin E2-prostaglandin E receptor subtype 4 (EP4) signaling mediates UV irradiation-induced systemic immunosuppression. Proc Natl Acad Sci U S A 108(16):6668–6673PubMedCrossRef
110.
Zurück zum Zitat Pinchuk IV, Beswick EJ, Saada JI, Boya G, Schmitt D et al (2011) Human colonic myofibroblasts promote expansion of CD4+ CD25high Foxp3+ regulatory T cells. Gastroenterology 140(7):2019–2030PubMedCrossRef Pinchuk IV, Beswick EJ, Saada JI, Boya G, Schmitt D et al (2011) Human colonic myofibroblasts promote expansion of CD4+ CD25high Foxp3+ regulatory T cells. Gastroenterology 140(7):2019–2030PubMedCrossRef
111.
Zurück zum Zitat Gabrilovich DI, Nagaraj S (2009) Myeloid-derived suppressor cells as regulators of the immune system. Nat Rev Immunol 9(3):162–174PubMedCrossRef Gabrilovich DI, Nagaraj S (2009) Myeloid-derived suppressor cells as regulators of the immune system. Nat Rev Immunol 9(3):162–174PubMedCrossRef
112.
Zurück zum Zitat Lu T, Gabrilovich DI. (2012) Molecular Pathways : Tumor Infiltrating Myeloid Cells and Reactive Oxygen Species in Regulation of Tumor Microenvironment. Clin Cancer Res Off J Am Assoc Cancer Res 18(18):1–6 Lu T, Gabrilovich DI. (2012) Molecular Pathways : Tumor Infiltrating Myeloid Cells and Reactive Oxygen Species in Regulation of Tumor Microenvironment. Clin Cancer Res Off J Am Assoc Cancer Res 18(18):1–6
113.
Zurück zum Zitat Gabrilovich DI, Ostrand-Rosenberg S, Bronte V (2012) Coordinated regulation of myeloid cells by tumours. Nat Rev Immunol 12(4):253–268PubMedCrossRef Gabrilovich DI, Ostrand-Rosenberg S, Bronte V (2012) Coordinated regulation of myeloid cells by tumours. Nat Rev Immunol 12(4):253–268PubMedCrossRef
114.
Zurück zum Zitat Obermajer N, Muthuswamy R, Lesnock J, Edwards RP, Kalinski P (2011) Positive feedback between PGE2 and COX2 redirects the differentiation of human dendritic cells toward stable myeloid-derived suppressor cells. Blood 118(20):5498–5505PubMedCrossRef Obermajer N, Muthuswamy R, Lesnock J, Edwards RP, Kalinski P (2011) Positive feedback between PGE2 and COX2 redirects the differentiation of human dendritic cells toward stable myeloid-derived suppressor cells. Blood 118(20):5498–5505PubMedCrossRef
115.
Zurück zum Zitat Obermajer N, Muthuswamy R, Odunsi K, Edwards RP, Kalinski P (2011) PGE(2)-induced CXCL12 production and CXCR4 expression controls the accumulation of human MDSCs in ovarian cancer environment. Cancer Res 71(24):7463–7470PubMedCrossRef Obermajer N, Muthuswamy R, Odunsi K, Edwards RP, Kalinski P (2011) PGE(2)-induced CXCL12 production and CXCR4 expression controls the accumulation of human MDSCs in ovarian cancer environment. Cancer Res 71(24):7463–7470PubMedCrossRef
116.
Zurück zum Zitat Sinha P, Clements VK, Fulton AM, Ostrand-Rosenberg S (2007) Prostaglandin E2 promotes tumor progression by inducing myeloid-derived suppressor cells. Cancer Res 67(9):4507–4513PubMedCrossRef Sinha P, Clements VK, Fulton AM, Ostrand-Rosenberg S (2007) Prostaglandin E2 promotes tumor progression by inducing myeloid-derived suppressor cells. Cancer Res 67(9):4507–4513PubMedCrossRef
117.
Zurück zum Zitat Rodriguez PC, Ernstoff MS, Hernandez C, Atkins M, Zabaleta J et al (2009) Arginase I-producing myeloid-derived suppressor cells in renal cell carcinoma are a subpopulation of activated granulocytes. Cancer Res 69(4):1553–1560PubMedCrossRef Rodriguez PC, Ernstoff MS, Hernandez C, Atkins M, Zabaleta J et al (2009) Arginase I-producing myeloid-derived suppressor cells in renal cell carcinoma are a subpopulation of activated granulocytes. Cancer Res 69(4):1553–1560PubMedCrossRef
118.
Zurück zum Zitat Li Y, Yin S, Nie D, Xie S, Ma L et al (2011) MK886 inhibits the proliferation of HL-60 leukemia cells by suppressing the expression of mPGES-1 and reducing prostaglandin E2 synthesis. Int J Hematol 94(5):472–478PubMedCrossRef Li Y, Yin S, Nie D, Xie S, Ma L et al (2011) MK886 inhibits the proliferation of HL-60 leukemia cells by suppressing the expression of mPGES-1 and reducing prostaglandin E2 synthesis. Int J Hematol 94(5):472–478PubMedCrossRef
119.
Zurück zum Zitat Deckmann K, Rorsch F, Geisslinger G, Grosch S (2012) Dimethylcelecoxib induces an inhibitory complex consisting of HDAC1/NF-kappaB(p65)RelA leading to transcriptional downregulation of mPGES-1 and EGR1. Cell Signal 24(2):460–467PubMedCrossRef Deckmann K, Rorsch F, Geisslinger G, Grosch S (2012) Dimethylcelecoxib induces an inhibitory complex consisting of HDAC1/NF-kappaB(p65)RelA leading to transcriptional downregulation of mPGES-1 and EGR1. Cell Signal 24(2):460–467PubMedCrossRef
120.
Zurück zum Zitat Deckmann K, Rorsch F, Steri R, Schubert-Zsilavecz M, Geisslinger G et al (2010) Dimethylcelecoxib inhibits mPGES-1 promoter activity by influencing EGR1 and NF-kappaB. Biochem Pharmacol 80(9):1365–1372PubMedCrossRef Deckmann K, Rorsch F, Steri R, Schubert-Zsilavecz M, Geisslinger G et al (2010) Dimethylcelecoxib inhibits mPGES-1 promoter activity by influencing EGR1 and NF-kappaB. Biochem Pharmacol 80(9):1365–1372PubMedCrossRef
121.
Zurück zum Zitat Koeberle A, Siemoneit U, Buhring U, Northoff H, Laufer S et al (2008) Licofelone suppresses prostaglandin E2 formation by interference with the inducible microsomal prostaglandin E2 synthase-1. J Pharmacol Exp Ther 326(3):975–982PubMedCrossRef Koeberle A, Siemoneit U, Buhring U, Northoff H, Laufer S et al (2008) Licofelone suppresses prostaglandin E2 formation by interference with the inducible microsomal prostaglandin E2 synthase-1. J Pharmacol Exp Ther 326(3):975–982PubMedCrossRef
122.
Zurück zum Zitat Cote B, Boulet L, Brideau C, Claveau D, Ethier D et al (2007) Substituted phenanthrene imidazoles as potent, selective, and orally active mPGES-1 inhibitors. Bioorg Med Chem Lett 17(24):6816–6820PubMedCrossRef Cote B, Boulet L, Brideau C, Claveau D, Ethier D et al (2007) Substituted phenanthrene imidazoles as potent, selective, and orally active mPGES-1 inhibitors. Bioorg Med Chem Lett 17(24):6816–6820PubMedCrossRef
123.
Zurück zum Zitat Giroux A, Boulet L, Brideau C, Chau A, Claveau D et al (2009) Discovery of disubstituted phenanthrene imidazoles as potent, selective and orally active mPGES-1 inhibitors. Bioorg Med Chem Lett 19(20):5837–5841PubMedCrossRef Giroux A, Boulet L, Brideau C, Chau A, Claveau D et al (2009) Discovery of disubstituted phenanthrene imidazoles as potent, selective and orally active mPGES-1 inhibitors. Bioorg Med Chem Lett 19(20):5837–5841PubMedCrossRef
124.
Zurück zum Zitat Chini MG, De Simone R, Bruno I, Riccio R, Dehm F et al (2012) Design and synthesis of a second series of triazole-based compounds as potent dual mPGES-1 and 5-lipoxygenase inhibitors. Eur J Med Chem 54:311–323PubMedCrossRef Chini MG, De Simone R, Bruno I, Riccio R, Dehm F et al (2012) Design and synthesis of a second series of triazole-based compounds as potent dual mPGES-1 and 5-lipoxygenase inhibitors. Eur J Med Chem 54:311–323PubMedCrossRef
125.
Zurück zum Zitat Beales IL, Ogunwobi OO (2010) Microsomal prostaglandin E synthase-1 inhibition blocks proliferation and enhances apoptosis in oesophageal adenocarcinoma cells without affecting endothelial prostacyclin production. Int J Cancer J Int Cancer 126(9):2247–2255 Beales IL, Ogunwobi OO (2010) Microsomal prostaglandin E synthase-1 inhibition blocks proliferation and enhances apoptosis in oesophageal adenocarcinoma cells without affecting endothelial prostacyclin production. Int J Cancer J Int Cancer 126(9):2247–2255
126.
Zurück zum Zitat Chang HH, Meuillet EJ (2011) Identification and development of mPGES-1 inhibitors: where we are at? Future Med Chem 3(15):1909–1934PubMedCrossRef Chang HH, Meuillet EJ (2011) Identification and development of mPGES-1 inhibitors: where we are at? Future Med Chem 3(15):1909–1934PubMedCrossRef
127.
Zurück zum Zitat Moon Y, Glasgow WC, Eling TE (2005) Curcumin suppresses interleukin 1beta-mediated microsomal prostaglandin E synthase 1 by altering early growth response gene 1 and other signaling pathways. J Pharmacol Exp Ther 315(2):788–795PubMedCrossRef Moon Y, Glasgow WC, Eling TE (2005) Curcumin suppresses interleukin 1beta-mediated microsomal prostaglandin E synthase 1 by altering early growth response gene 1 and other signaling pathways. J Pharmacol Exp Ther 315(2):788–795PubMedCrossRef
128.
Zurück zum Zitat Koeberle A, Northoff H, Werz O (2009) Curcumin blocks prostaglandin E2 biosynthesis through direct inhibition of the microsomal prostaglandin E2 synthase-1. Mol Cancer Ther 8(8):2348–2355PubMedCrossRef Koeberle A, Northoff H, Werz O (2009) Curcumin blocks prostaglandin E2 biosynthesis through direct inhibition of the microsomal prostaglandin E2 synthase-1. Mol Cancer Ther 8(8):2348–2355PubMedCrossRef
129.
Zurück zum Zitat Koeberle A, Bauer J, Verhoff M, Hoffmann M, Northoff H et al (2009) Green tea epigallocatechin-3-gallate inhibits microsomal prostaglandin E(2) synthase-1. Biochem Biophys Res Commun 388(2):350–354PubMedCrossRef Koeberle A, Bauer J, Verhoff M, Hoffmann M, Northoff H et al (2009) Green tea epigallocatechin-3-gallate inhibits microsomal prostaglandin E(2) synthase-1. Biochem Biophys Res Commun 388(2):350–354PubMedCrossRef
130.
Zurück zum Zitat Koeberle A, Pollastro F, Northoff H, Werz O (2009) Myrtucommulone, a natural acylphloroglucinol, inhibits microsomal prostaglandin E(2) synthase-1. Br J Pharmacol 156(6):952–961PubMedCrossRef Koeberle A, Pollastro F, Northoff H, Werz O (2009) Myrtucommulone, a natural acylphloroglucinol, inhibits microsomal prostaglandin E(2) synthase-1. Br J Pharmacol 156(6):952–961PubMedCrossRef
131.
Zurück zum Zitat Balkwill F, Mantovani A (2001) Inflammation and cancer: back to Virchow? Lancet 357(9255):539–545PubMedCrossRef Balkwill F, Mantovani A (2001) Inflammation and cancer: back to Virchow? Lancet 357(9255):539–545PubMedCrossRef
132.
Zurück zum Zitat Aggarwal BB, Gehlot P (2009) Inflammation and cancer: how friendly is the relationship for cancer patients? Curr Opin Pharmacol 9(4):351–369PubMedCrossRef Aggarwal BB, Gehlot P (2009) Inflammation and cancer: how friendly is the relationship for cancer patients? Curr Opin Pharmacol 9(4):351–369PubMedCrossRef
133.
Zurück zum Zitat Waldner MJ, Neurath MF (2009) Colitis-associated cancer: the role of T cells in tumor development. Semin Immunopathol 31(2):249–256PubMedCrossRef Waldner MJ, Neurath MF (2009) Colitis-associated cancer: the role of T cells in tumor development. Semin Immunopathol 31(2):249–256PubMedCrossRef
134.
Zurück zum Zitat Lewis JD, Deren JJ, Lichtenstein GR (1999) Cancer risk in patients with inflammatory bowel disease. Gastroenterol Clin N Am 28(2):459–477, xCrossRef Lewis JD, Deren JJ, Lichtenstein GR (1999) Cancer risk in patients with inflammatory bowel disease. Gastroenterol Clin N Am 28(2):459–477, xCrossRef
135.
Zurück zum Zitat Herrinton LJ, Liu L, Levin TR, Allison JE, Lewis JD et al (2012) Incidence and mortality of colorectal adenocarcinoma in persons with inflammatory bowel disease from 1998 to 2010. Gastroenterology 143(2):382–389PubMedCrossRef Herrinton LJ, Liu L, Levin TR, Allison JE, Lewis JD et al (2012) Incidence and mortality of colorectal adenocarcinoma in persons with inflammatory bowel disease from 1998 to 2010. Gastroenterology 143(2):382–389PubMedCrossRef
136.
Zurück zum Zitat Ullman TA, Itzkowitz SH (2011) Intestinal inflammation and cancer. Gastroenterology 140(6):1807–1816PubMedCrossRef Ullman TA, Itzkowitz SH (2011) Intestinal inflammation and cancer. Gastroenterology 140(6):1807–1816PubMedCrossRef
137.
Zurück zum Zitat Dvorak HF (1986) Tumors: wounds that do not heal. Similarities between tumor stroma generation and wound healing. N Engl J Med 315(26):1650–1659PubMedCrossRef Dvorak HF (1986) Tumors: wounds that do not heal. Similarities between tumor stroma generation and wound healing. N Engl J Med 315(26):1650–1659PubMedCrossRef
138.
Zurück zum Zitat Schafer M, Werner S (2008) Cancer as an overhealing wound: an old hypothesis revisited. Nat Rev Mol Cell Biol 9(8):628–638PubMedCrossRef Schafer M, Werner S (2008) Cancer as an overhealing wound: an old hypothesis revisited. Nat Rev Mol Cell Biol 9(8):628–638PubMedCrossRef
139.
Zurück zum Zitat Hong KH, Bonventre JC, O'Leary E, Bonventre JV, Lander ES (2001) Deletion of cytosolic phospholipase A(2) suppresses Apc(Min)-induced tumorigenesis. Proc Natl Acad Sci U S A 98(7):3935–3939PubMedCrossRef Hong KH, Bonventre JC, O'Leary E, Bonventre JV, Lander ES (2001) Deletion of cytosolic phospholipase A(2) suppresses Apc(Min)-induced tumorigenesis. Proc Natl Acad Sci U S A 98(7):3935–3939PubMedCrossRef
140.
Zurück zum Zitat Chulada PC, Thompson MB, Mahler JF, Doyle CM, Gaul BW et al (2000) Genetic disruption of Ptgs-1, as well as Ptgs-2, reduces intestinal tumorigenesis in Min mice. Cancer Res 60(17):4705–4708PubMed Chulada PC, Thompson MB, Mahler JF, Doyle CM, Gaul BW et al (2000) Genetic disruption of Ptgs-1, as well as Ptgs-2, reduces intestinal tumorigenesis in Min mice. Cancer Res 60(17):4705–4708PubMed
141.
Zurück zum Zitat Ishikawa TO, Herschman HR (2010) Tumor formation in a mouse model of colitis-associated colon cancer does not require COX-1 or COX-2 expression. Carcinogenesis 31(4):729–736PubMedCrossRef Ishikawa TO, Herschman HR (2010) Tumor formation in a mouse model of colitis-associated colon cancer does not require COX-1 or COX-2 expression. Carcinogenesis 31(4):729–736PubMedCrossRef
142.
Zurück zum Zitat Oshima M, Dinchuk JE, Kargman SL, Oshima H, Hancock B et al (1996) Suppression of intestinal polyposis in Apc delta716 knockout mice by inhibition of cyclooxygenase 2 (COX-2). Cell 87(5):803–809PubMedCrossRef Oshima M, Dinchuk JE, Kargman SL, Oshima H, Hancock B et al (1996) Suppression of intestinal polyposis in Apc delta716 knockout mice by inhibition of cyclooxygenase 2 (COX-2). Cell 87(5):803–809PubMedCrossRef
143.
Zurück zum Zitat Elander N, Ungerback J, Olsson H, Uematsu S, Akira S et al (2008) Genetic deletion of mPGES-1 accelerates intestinal tumorigenesis in APC(Min/+) mice. Biochem Biophys Res Commun 372(1):249–253PubMedCrossRef Elander N, Ungerback J, Olsson H, Uematsu S, Akira S et al (2008) Genetic deletion of mPGES-1 accelerates intestinal tumorigenesis in APC(Min/+) mice. Biochem Biophys Res Commun 372(1):249–253PubMedCrossRef
144.
Zurück zum Zitat Sasaki Y, Kamei D, Ishikawa Y, Ishii T, Uematsu S et al (2012) Microsomal prostaglandin E synthase-1 is involved in multiple steps of colon carcinogenesis. Oncogene 31(24):2943–2952PubMedCrossRef Sasaki Y, Kamei D, Ishikawa Y, Ishii T, Uematsu S et al (2012) Microsomal prostaglandin E synthase-1 is involved in multiple steps of colon carcinogenesis. Oncogene 31(24):2943–2952PubMedCrossRef
145.
Zurück zum Zitat Okuyama T, Ishihara S, Sato H, Rumi MA, Kawashima K et al (2002) Activation of prostaglandin E2-receptor EP2 and EP4 pathways induces growth inhibition in human gastric carcinoma cell lines. J Lab Clin Med 140(2):92–102PubMed Okuyama T, Ishihara S, Sato H, Rumi MA, Kawashima K et al (2002) Activation of prostaglandin E2-receptor EP2 and EP4 pathways induces growth inhibition in human gastric carcinoma cell lines. J Lab Clin Med 140(2):92–102PubMed
146.
Zurück zum Zitat Liu CH, Chang SH, Narko K, Trifan OC, Wu MT et al (2001) Overexpression of cyclooxygenase-2 is sufficient to induce tumorigenesis in transgenic mice. J Biol Chem 276(21):18563–18569PubMedCrossRef Liu CH, Chang SH, Narko K, Trifan OC, Wu MT et al (2001) Overexpression of cyclooxygenase-2 is sufficient to induce tumorigenesis in transgenic mice. J Biol Chem 276(21):18563–18569PubMedCrossRef
147.
Zurück zum Zitat Howe LR, Chang SH, Tolle KC, Dillon R, Young LJ et al (2005) HER2/neu-induced mammary tumorigenesis and angiogenesis are reduced in cyclooxygenase-2 knockout mice. Cancer Res 65(21):10113–10119PubMedCrossRef Howe LR, Chang SH, Tolle KC, Dillon R, Young LJ et al (2005) HER2/neu-induced mammary tumorigenesis and angiogenesis are reduced in cyclooxygenase-2 knockout mice. Cancer Res 65(21):10113–10119PubMedCrossRef
148.
Zurück zum Zitat Sung YM, He G, Fischer SM (2005) Lack of expression of the EP2 but not EP3 receptor for prostaglandin E2 results in suppression of skin tumor development. Cancer Res 65(20):9304–9311PubMedCrossRef Sung YM, He G, Fischer SM (2005) Lack of expression of the EP2 but not EP3 receptor for prostaglandin E2 results in suppression of skin tumor development. Cancer Res 65(20):9304–9311PubMedCrossRef
Metadaten
Titel
Multifaceted roles of PGE2 in inflammation and cancer
verfasst von
Masako Nakanishi
Daniel W. Rosenberg
Publikationsdatum
01.03.2013
Verlag
Springer-Verlag
Erschienen in
Seminars in Immunopathology / Ausgabe 2/2013
Print ISSN: 1863-2297
Elektronische ISSN: 1863-2300
DOI
https://doi.org/10.1007/s00281-012-0342-8

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