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Cyclooxygenase-2 and Chronic Inflammation: Drivers of Colorectal Tumorigenesis

  • Monica M. Bertagnolli
Chapter
Part of the Energy Balance and Cancer book series (EBAC, volume 4)

Abstract

A common feature of the relationship between abnormal energy balance, altered hormonal regulation, and cancer is the presence of increased inflammation. In individuals with obesity-associated metabolic disorder, an increased inflammatory response can be identified on both systemic- and tissue-specific levels. This chapter details the relationship between cyclooxygenase-2 (COX-2), a key mediator of local inflammatory response, and the development of colorectal cancer. It also describes the modulation of COX-2 activity as a means of preventing and treating colorectal tumors. Finally, this chapter addresses new data concerning the role of COX-2 activity in obesity and metabolic syndrome.

Keywords

Epidermal Growth Factor Receptor Familial Adenomatous Polyposis Colorectal Neoplasia Advanced Adenoma Nonselective NSAID 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    Waddell WR, Loughry RW (1983) Sulindac for polyposis of the colon. J Surg Oncol 24(1):83–87PubMedGoogle Scholar
  2. 2.
    Giardiello FM, Hamilton SR, Krush AJ, Piantadosi S, Hylind LM, Celano P et al (1993) Treatment of colonic and rectal adenomas with sulindac in familial adenomatous polyposis. N Eng J Med 328:1313–1316Google Scholar
  3. 3.
    Giardiello FM, Yang VW, Hylind LM, Krush AJ, Petersen GM, Trimbath JD et al (2002) Primary chemoprevention of familial adenomatous polyposis with sulindac. N Engl J Med 346(14):1054–1059PubMedGoogle Scholar
  4. 4.
    Labayle D, Fischer D, Vielh P, Drouhin F, Pariente A, Bories C et al (1991) Sulindac causes regression of rectal polyps in familial adenomatous polyposis. Gastroenterology 101:635–639PubMedGoogle Scholar
  5. 5.
    Phillips RK, Wallace MH, Lynch P, Hawk E, Gordon GB, Saunders B et al (2002) A randomised, double-blind, placebo-controlled study of celecoxib, a selective cyclooxygenase-2 inhibitor, on duodenal polyposis in familial adenomatous polyposis. Gut 50(6):857–860PubMedGoogle Scholar
  6. 6.
    Nugent KP, Farmer KC, Spigelman AD, Williams CB, Phillips RK (1993) Randomized controlled trial of the effect of sulindac on duodenal and rectal polyposis and cell proliferation in patients with familial adenomatous polyposis. Br J Surg 80(12):1618–1619PubMedGoogle Scholar
  7. 7.
    Waddell WR, Ganser GF, Cerise EJ, Loughry RW (1989) Sulindac for polyposis of the colon. Am J Surg 157:175–179PubMedGoogle Scholar
  8. 8.
    Arber N, Eagle CJ, Spicak J, Racz I, Dite P, Hajer J et al (2006) Celecoxib for the prevention of colorectal adenomatous polyps. N Eng J Med 355(9):885–895Google Scholar
  9. 9.
    Baron JA, Cole BF, Sandler RS, Haile RW, Ahnen D, Bressalier R et al (2003) A randomized trial of aspirin to prevent colorectal adenomas. N Engl J Med 348(10):891–899PubMedGoogle Scholar
  10. 10.
    Benamouzig R, Deyra J, Martin A, Girard B, Jullian E, Piednoir B et al (2003) Daily soluble aspirin and prevention of colorectal adenoma recurrence: one-year results of the APACC trial. Gastroenterology 125(2):612–614Google Scholar
  11. 11.
    Bertagnolli MM, Eagle CJ, Zauber AG, Redston M, Solomon SD, Kim K et al (2006) A randomized trial of celecoxib to prevent sporadic colorectal adenomas. N Engl J Med 355:873–884PubMedGoogle Scholar
  12. 12.
    Bucher C, Jordan P, Nickeleit V, Torhorst J, Mihatsch MJ (1999) Relative risk of malignant tumors in analgesic abusers. Effects of long- term intake of aspirin. Clin Nephrol 51(2):67–72PubMedGoogle Scholar
  13. 13.
    Egan KM, Stampfer MJ, Giovannucci E, Rosner BA, Colditz GA (1996) Prospective study of regular aspirin use and the risk of breast cancer. J Natl Cancer Inst 88(14):988–993PubMedGoogle Scholar
  14. 14.
    Farrow DC, Vaughan TL, Hansten PD, Stanford JL, Risch HA, Gammon MD et al (1998) Use of aspirin and other nonsteroidal anti-inflammatory drugs and risk of esophageal and gastric cancer. Cancer Epidemiol Biomarkers Prev 7(2):97–102PubMedGoogle Scholar
  15. 15.
    Garcia-Rodriguez LA, Heuerta-Alvarez C (2001) Reduced risk of colorectal cancer among long-term users of aspirin and nonaspirin nonsteroidal antiinflammatory drugs. Epidemiology 12:88–93PubMedGoogle Scholar
  16. 16.
    Giovannucci E, Rimm EB, Stampfer MJ, Colditz GA, Ascherio A, Willett WC (1994) Aspirin use and the risk for colorectal cancer and adenoma in male health professionals. Ann Intern Med 121(4):241–246PubMedGoogle Scholar
  17. 17.
    Hixson LJ, Earnest DL, Fennerty MB, Sampliner RE (1993) NSAID effect on sporadic colon polyps. Am J Gastroenterol 88(10):1652–1656PubMedGoogle Scholar
  18. 18.
    Langman MJ, Cheng KK, Gilman EA, Lancashire RJ (2000) Effect of anti-inflammatory drugs on overall risk of common cancer: case-control study in general practice research database. BMJ 320(7250):1642–1646PubMedGoogle Scholar
  19. 19.
    Thun MJ, Namboodiri MM, Heath CW Jr (1991) Aspirin use and reduced risk of fatal colon cancer. N Engl J Med 325(23):1593–1596PubMedGoogle Scholar
  20. 20.
    Ghosh N, Chaki R, Mandal V, Mandal SC (2010) COX-2 as a target for cancer chemotherapy. Pharmacol Rep 62:233–244PubMedGoogle Scholar
  21. 21.
    Koki AT, Leahy KM, Masferrer JL (1999) Potential utility of COX-2 inhibitors in chemoprevention and chemotherapy. Expert Opin Investig Drugs 8(10):1623–1638PubMedGoogle Scholar
  22. 22.
    Subbaramaiah K, Dannenberg AJ (2003) Cyclooxygenase 2: a molecular target for cancer prevention and treatment. Trends Pharmacol Sci 24(2):96–102PubMedGoogle Scholar
  23. 23.
    Grosser T, Yu Y, FitzGerald GA (2010) Emotion recollected in tranquility: lessons learned from the COX-2 saga. Annu Rev Med 61:17–33PubMedGoogle Scholar
  24. 24.
    Bertagnolli MM. Eicosanoids (2006) In: Shepro D, editor. Microvascular research: biology and pathology. Elsevier, San Diego, CA, p 727Google Scholar
  25. 25.
    Surh I, Rundhaug J, Pavone A, Mikulec C, Abel E, Fischer SM (2011) Upregulation of the EP1 receptor for prostaglandin E2 promotes skin tumor progression. Mol Carcinog 50(6):458–468PubMedGoogle Scholar
  26. 26.
    Balch CM, Dougherty PA, Tilden AB (1982) Excessive prostaglandin E2 production by suppressor monocytes in head and neck cancer patients. Ann Surg 196:645–650PubMedGoogle Scholar
  27. 27.
    Bennett A, Tacca MD, Stamford IF, Zebro T (1977) Prostaglandins from tumour of human large bowel. Br J Cancer 6:881–884Google Scholar
  28. 28.
    O’Banion MK, Sadowski HB, Winn V, Young DA (1991) A serum- and glucocorticoid-regulated 4-kilobase mRNA encodes a cyclooxygenase-related protein. J Biol Chem 266(34):23261–23267PubMedGoogle Scholar
  29. 29.
    Marnett LJ, DuBois RN (2002) COX-2: a target for colon cancer prevention. Annu Rev Pharmacol Toxicol 42:55–80PubMedGoogle Scholar
  30. 30.
    Smith WL, Garavito RM, DeWitt DL (1996) Prostaglandin endoperoxide H synthases (cyclooxygenases)-1 and -2. J Biol Chem 271(52):33157–33160PubMedGoogle Scholar
  31. 31.
    Williams CS, DuBois RN (1996) Prostaglandin endoperoxide synthase: why two isoforms? Am J Physiol 270(3 Pt 1):G393–G400PubMedGoogle Scholar
  32. 32.
    Herschman HR (1996) Prostaglandin synthase 2. Biochim Biophys Acta 1299(1):125–140PubMedGoogle Scholar
  33. 33.
    Howe LR, Subbaramaiah K, Brown AM, Dannenberg AJ (2001) Cyclooxygenase-2: a target for the prevention and treatment of breast cancer. Endocr Relat Cancer 8(2):97–114PubMedGoogle Scholar
  34. 34.
    Herschman HR (1999) Function and regulation of prostaglandin synthase 2. Adv Exp Med Biol 469:3–8PubMedGoogle Scholar
  35. 35.
    Stappenbeck TS, Miyoshi H (2009) The role of stromal stem cells in tissue regeneration and wound repair. Science 324:1666–1669PubMedGoogle Scholar
  36. 36.
    Eberhart CE, Coffey RJ, Radhika A, Giardiello FM, Ferrenbach S, DuBois RN (1994) Up-regulation of cyclooxygenase 2 gene expression in human colorectal adenomas and adenocarcinomas. Gastroenterology 107(4):1183–1188PubMedGoogle Scholar
  37. 37.
    Sheehan KM, Sheahan K, O’Donoghue DP, MacSweeney F, Conroy RM, Fitzgerald DJ et al (1999) The relationship between cyclooxygenase-2 expression and colorectal cancer. JAMA 282(13):1254–1257PubMedGoogle Scholar
  38. 38.
    Masunaga R, Kohno H, Dhar DK, Ohno S, Shibakita M, Kinugasa S et al (2000) Cyclooxygenase-2 expression correlates with tumor neovascularization and prognosis in human colorectal carcinoma patients. Clin Cancer Res 6(10):4064–4068PubMedGoogle Scholar
  39. 39.
    Tomozawa S, Tsuno NH, Sunami E, Hatano K, Kitayama J, Osada T et al (2000) Cyclooxygenase-2 overexpression correlates with tumour recurrence, especially haematogenous metastasis, of colorectal cancer. Br J Cancer 83(3):324–328PubMedGoogle Scholar
  40. 40.
    Oshima M, Dinchuk JE, Kargman SL, Oshima H, Hancock B, Kwong E (1996) Suppression of intestinal polyposis in Apc delta knockout mice by inhibition of cyclooxygenase 2 (COX-2). Cell 87:803–809PubMedGoogle Scholar
  41. 41.
    Sheng H, Shao J, Morrow JD, Beauchamp RD, DuBois RN (1998) Modulation of apoptosis and Bcl-2 expression by prostaglandin E2 in human colon cancer cells. Cancer Res 58:362–366PubMedGoogle Scholar
  42. 42.
    Xie W, Herschman HR (1995) v-src induces prostaglandin synthase 2 gene expression by activation of the c-Jun N-terminal kinase and the c-Jun transcription factor. J Biol Chem 270(46):27622–27628PubMedGoogle Scholar
  43. 43.
    Subbaramaiah K, Norton L, Gerald W, Dannenberg AJ. Increased expression of cyclooxygenase-2 in HER-2-overexpressing human breast cancer cells. NCI 7th SPORE Investigators’ Workshop, Bethesda, MDGoogle Scholar
  44. 44.
    Vadlamudi R, Mandal M, Adam L, Steinbach G, Mendelsohn J, Kumar R (1999) Regulation of cyclooxygenase-2 pathway by HER2 receptor. Oncogene 18(2):305–314PubMedGoogle Scholar
  45. 45.
    Chen G, Wilson R, McKillop JH, Walker JJ (1994) The role of cytokines in the production of prostacyclin and thromboxane in human mononuclear cells. Immunol Invest 23(4–5):269–279PubMedGoogle Scholar
  46. 46.
    Subbaramaiah K, Telang N, Ramonetti JT, Araki R, DeVito B, Weksler BB et al (1996) Transcription of cyclooxygenase-2 is enhanced in transformed mammary epithelial cells. Cancer Res 56(19):4424–4429PubMedGoogle Scholar
  47. 47.
    Subbarayan V, Sabichi AL, Llansa N, Lippman SM, Menter DG (2001) Differential expression of cyclooxygenase-2 and its regulation by tumor necrosis factor-alpha in normal and malignant prostate cells. Cancer Res 61(6):2720–2726PubMedGoogle Scholar
  48. 48.
    Bonazzi A, Mastyugin V, Mieyal PA, Dunn MW, Laniado-Schwartzman M (2000) Regulation of cyclooxygenase-2 by hypoxia and peroxisome proliferators in the corneal epithelium. J Biol Chem 275:2837–2844PubMedGoogle Scholar
  49. 49.
    Bazan NG, Lukiw WJ (2002) Cyclooxygenase-2 and presenilin-1 gene expression induced by interleukin-1beta and amyloid beta 42 peptide is potentiated by hypoxia in primary human neural cells. J Biol Chem 277:30359–30367PubMedGoogle Scholar
  50. 50.
    Kopan R, Ilagan MX (2009) The canonical Notch signaling pathway: unfolding the activation mechanism. Cell 137:216–233PubMedGoogle Scholar
  51. 51.
    Xie W, Herschman HR (1996) Transcriptional regulation of prostaglandin synthase 2 gene expression by platelet-derived growth factor and serum. J Biol Chem 271(49):31742–31748PubMedGoogle Scholar
  52. 52.
    Subbaramaiah K, Chung WJ, Dannenberg AJ (1998) Ceramide regulates the transcription of cyclooxygenase-2. Evidence for involvement of extracellular signal-regulated kinase/c-Jun N-terminal kinase and p38 mitogen-activated protein kinase pathways. J Biol Chem 273(49):32943–32949PubMedGoogle Scholar
  53. 53.
    Chen C-C, Sun Y-T, Chen J-J, Chang Y-J (2001) Tumor necrosis factor-alpha-induced cyclooxygenase-2 expression via sequential activation of ceramide-dependent mitogen-activated protein kinases, and I-kappaB kinase 1/2 in human alveolar epithelial cells. Mol Pharmacol 59(3):493–500PubMedGoogle Scholar
  54. 54.
    Cok SJ, Morrison AR (2001) The 3′-untranslated region of murine cyclooxygenase-2 contains multiple regulatory elements that alter message stability and translational efficiency. J Biol Chem 276(25):23179–23185PubMedGoogle Scholar
  55. 55.
    Dixon DA, Tolley ND, King PH, Nabors LB, McIntyre TM, Zimmerman GA et al (2001) Altered expression of the mRNA stability factor HuR promotes cyclooxygenase-2 expression in colon cancer cells. J Clin Invest 108(11):1657–1665PubMedGoogle Scholar
  56. 56.
    Strillacci A, Griffoni C, Sansone P, Paterini P, Piazzi G, Lazzarini G et al (2009) MiR-101 downregulation is involved in cyclooxygenase-2 overexpression in human colon cancer cells. Exp Cell Res 315:1439–1447PubMedGoogle Scholar
  57. 57.
    Bianchini F, Kaaks R, Vainio H (2002) Overweight, obesity, and cancer risk. Lancet Oncol 3(9):565–574PubMedGoogle Scholar
  58. 58.
    Calle EE, Rodriguez C, Walker-Thurmond K, Thun MJ (2003) Overweight, obesity, and morality from cancer in a prospectively studied cohort of U.S. adults. N Engl J Med 348(17):1625–1638PubMedGoogle Scholar
  59. 59.
    Delage B, Rullier A, Capdepont M, Rullier E, Cassand P (2007) The effect of body weight on altered expression of nuclear receptors and cyclooxygenase-2 in human colorectal cancers. Nutr J 6(20):1475–2891Google Scholar
  60. 60.
    Ghoshal S, Trivedi DB, Graf GA, Loftin CD (2011) Cyclooxygenase-2 deficiency attenuates adipose tissue differentiation and inflammation in mice. J Biol Chem 286(1):889–898PubMedGoogle Scholar
  61. 61.
    Vegiopoulos A, Muller-Decker K, Strzoda D, Schmitt I, Chichelnitskiy E, Ostertag A et al (2010) Cyclooxygenase-2 controls energy homeostasis in mice by de novo recruitment of brown adipocytes. Science 328:1158–1161PubMedGoogle Scholar
  62. 62.
    McDougall CJ, Ngoi SS, Goldman IS, Godwin T, Felix J, DeCosse JJ et al (1990) Reduced expression of HLA class I and II antigens in colon cancer. Cancer Res 50(24):8023–8027PubMedGoogle Scholar
  63. 63.
    Harris SG, Padilla J, Koumas L, Ray D, Phipps RP (2002) Prostaglandins as modulators of immunity. Trands Immunol 23:144–150Google Scholar
  64. 64.
    Sheibanie AF, Yen JH, Kharullina T, Eming F, Zhang M, Tuma R 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 178:8138–8147PubMedGoogle Scholar
  65. 65.
    Yao C, Sakata D, Esaki Y, Li Y, Matsuoka T, Kuroiwa K et al (2009) Prostaglandin E2-EP4 signaling promotes immune inflammation through Th1 cell differentiation and Th17 cell expansion. Nat Med 15(6):633–640PubMedGoogle Scholar
  66. 66.
    Hixon LJ, Alaberts DX, Krutzsch M, Einsphar J, Brendel K, Gross PH et al (1994) Antiproliferative effect of nonsteroidal anti-inflammatory drugs against human colon cancer cells. Cancer Epidemiol Biomarkers Prev 3:433–438Google Scholar
  67. 67.
    Pai R, Nakamura T, Moon WS, Tarnawski AS (2003) Prostaglandins promote colon cancer cell invasion; signaling by cross-talk between two distinct growth factor receptors. FASEB J 17(12):1640–1647PubMedGoogle Scholar
  68. 68.
    Pai R, Sorgehan B, Szabo IL, Pavelka M, Baatar D, Tarnawski AS (2002) Prostaglandin E2 transactivates EGF receptor: a novel mechanism for promoting colon cancer growth and gastrointestinal hypertrophy. Nat Med 8(3):289–293PubMedGoogle Scholar
  69. 69.
    Castellone MD, Teramoto H, Williams BO, Druey KM, Gutkind JS (2005) Prostaglandin E2 promotes colon cancer cell growth through a novel Gs-axin-{beta}-catenin signaling axis. Science 310:1504–1510PubMedGoogle Scholar
  70. 70.
    Wang D, Buchanan FG, Wang H, Dey SK, DuBois RN (2005) Prostaglandin E2 enhances intestinal adenoma growth via activation of the Tas-mitogen-activated protein kinase cascade. Cancer Res 65:1822–1829PubMedGoogle Scholar
  71. 71.
    Wang D, Wang H, Shi Q, Katkuri S, Walhi W, Desvergne B et al (2004) Prostaglandin E(2) promotes colorectal adenoma growth via transactivation of the nuclear peroxisome proliferator-activated receptor delta. Cancer Cell 6(3):285–295PubMedGoogle Scholar
  72. 72.
    Kawamori T, Uchiya N, Sugimura T, Wakabayashi K (2003) Enhancement of colon carcinogenesis by prostaglandin E2 administration. Carcinogenesis 24:985–990PubMedGoogle Scholar
  73. 73.
    Su LK, Kinzler KW, Vogelstein B, Preisinger AC, Moser AR, Luongo C et al (1992) Multiple intestinal neoplasia caused by a mutation in the murine homolog of the APC gene. Science 256(5057):668–670PubMedGoogle Scholar
  74. 74.
    Myung SJ, Rerko RM, Yan M, Platzer P, Guda K, Dotson A et al (2006) 15-Hydroxyprostaglandin dehydrogenase is an in vivo suppressor of colon tumorigenesis. Proc Natl Acad Sci USA 103(32):12098–12102PubMedGoogle Scholar
  75. 75.
    Han C, Michalopolous GK, Wu T (2006) Prostaglandin E2 receptor EP1 transactivates EGFR/MET receptor tyrosine kinases and enhances invasiveness in human hepatocellular carcinoma cells. J Cell Physiol 207:261–270PubMedGoogle Scholar
  76. 76.
    Donnini S, Finetti F, Solito R, Terzuoli E, Sacchetti A, Morbidelli L et al (2007) EP2 prostanoid receptor promotes squamous cell carcinoma growth through epidermal growth factor receptor transactivation and iNOS and ERK1/2 pathways. FASEB J 21:2418–2430PubMedGoogle Scholar
  77. 77.
    Mendez M, LaPointe MC (2005) PGE2-induced hypertrophy of cardiac myocytes involves EP4 receptor-dependent activation of p42/44 MAPK and EGFR transactivation. Am J Physiol Heart Circ Physiol 288:H2111–H2117PubMedGoogle Scholar
  78. 78.
    Mutoh M, Watanabe K, Kitamura T, Shoji Y, Takahashi M, Kawamori T et al (2002) Involvement of prostaglandin E receptor subtype EP4 in colon carcinogenesis. Cancer Res 62:28–32PubMedGoogle Scholar
  79. 79.
    Watanabe K, Kawamori T, Nakatsugi S, Ohta T, Ohuchida S, Yamamoto H et al (1999) Role of the prostaglandin E receptor subtype EP1 in colon carcinogenesis. Cancer Res 59(20):5093–5096PubMedGoogle Scholar
  80. 80.
    Sonoshita M, Takaku K, Sasaki N, Sugimoto Y, Ushikubi F, Narumiya S et al (2001) Acceleration of intestinal polyposis through prostaglandin receptor EP2 in Apc(Delta 716) knockout mice. Nat Med 7(9):1048–1051PubMedGoogle Scholar
  81. 81.
    Wang D, Wang H, Brown J, Daikoku T, Ning W, Shi Q et al (2006) CXCL1 induced by prostaglandin E2 promotes angiogenesis in colorectal cancer. J Exp Med 203(4):941–951PubMedGoogle Scholar
  82. 82.
    Form DM, Auerbach R (1983) PGE2 and angiogenesis. Proc Soc Exp Biol Med 172:214–218PubMedGoogle Scholar
  83. 83.
    Gately S, Kerbel R (2003) Therapeutic potential of selective cyclooxygenase-2 inhibitors in the management of tumor angiogenesis. Prog Exp Tumor Res 37:179–192PubMedGoogle Scholar
  84. 84.
    Amano H, Hayashi I, Endo H et al (2003) Host prostaglandin E(2)-EP3 signaling regulates tumor-associated antiogenesis and tumor growth. J Exp Med 197:221–232PubMedGoogle Scholar
  85. 85.
    Niho N, Mutoh M, Kitamura T et al (2005) Suppression of azoxy-methane-induced colon cancer development in rats by a prostaglandin E receptor EP1-selective antagonist. Cancer Sci 96:260–264PubMedGoogle Scholar
  86. 86.
    Kawamori T, Kitamura T, Wantanabe K et al (2005) Prostaglandin E receptor subtype EP(1) deficiency inhibits colon cancer development. Carcinogenesis 26:353–357PubMedGoogle Scholar
  87. 87.
    Davids JS, Carothers AM, Damas BC, Bertagnolli MM (2010) Chronic cyclooxygenase-2 inhibition promotes myofibroblast-associated intestinal fibrosis. Cancer Prev Res 3(3):348–358Google Scholar
  88. 88.
    Powell DW, Adegboyege PA, Di Mari JF, Mifflin RC (2005) Epithelial cells and their neighbors. I. Role of intestinal myofibroblasts in development, repair, and cancer. Am J Physiol 289:G2–G7Google Scholar
  89. 89.
    Otte JM, Rosenberg IM, Podolsky DK (2003) Intestinal myofibroblasts in innate immune responses. Gastroenterology 124:1866–1878PubMedGoogle Scholar
  90. 90.
    Enders G (2007) Cyclooxygenase 2 overexpression abrogates the antiproliferative effects of TGF-beta. Br J Cancer 7:1388–1392Google Scholar
  91. 91.
    Buchanan FG, Wang D, Bargiacchi F et al (2003) Prostaglandin E2 regulates cell migration via the intracellular activation of the epidermal growth factor receptor. J Biol Chem 278:35451–35457PubMedGoogle Scholar
  92. 92.
    Tsujii M, DuBois RN (1995) Alterations in cellular adhesion and apoptosis in epithelial cells overexpressing prostaglandin endoperoxide synthase 2. Cell 83(3):493–501PubMedGoogle Scholar
  93. 93.
    Katajisto P, Vaahtomeri K, Ekman N, Ristimäki A, Bardeesy N, Feil R et al (2008) LKB1 signaling in mesenchymal cells is required for suppression of gastrointestinal polyposis. Nat Genet 40:455–459PubMedGoogle Scholar
  94. 94.
    Rakoff-Nahoum S, Medzhitov R (2007) Regulation of spontaneous intestinal tumorigenesis through the adaptor protein MyD88. Science 317:124–127PubMedGoogle Scholar
  95. 95.
    Yan M, Rerko RM, Paltzer P, Markowitz SD (2004) 15-hydorxyprostaglandin dehydrogenase, a Cox-2 oncogene antagonist, is a TGF-beta-induced suppressor of human gastrointestinal cancers. Proc Natl Acad Sci USA 101:17468–17473PubMedGoogle Scholar
  96. 96.
    Carothers AM, Davids JS, Damas BC, Bertagnolli MM (2010) Persistent cyclooxygenase-2 inhibition downregulates NF-kB, resulting in chronic intestinal inflammation in the Min/+ mouse model of colon tumorigenesis. Cancer Res 70(11):4433–4442PubMedGoogle Scholar
  97. 97.
    Greten FR, Arkan MC, Bollrath J, Hsu L-C, Goode J, Miething C et al (2007) NF-κB is a negative regulator of IL-1β secretion as revealed by genetic and pharmacological inhibition of IKKβ. Cell 130:918–931PubMedGoogle Scholar
  98. 98.
    Rouzer CA, Marnett LJ (2009) Cyclooxygenases: structural and functional insights. J Lipid Res 50 Suppl:S29–S34PubMedGoogle Scholar
  99. 99.
    Solomon SD, McMurray JJ, Pfeffer MA, Wittes J, Fowler R, Finn P et al (2005) Cardiovascular risk associated with celecoxib in a clinical trial for colorectal adenoma prevention. N Engl J Med 352(11):1071–1080PubMedGoogle Scholar
  100. 100.
    Hawkey CJ, Hawkey GM, Everitt S, Skelly MM, Stack WA, Gray D (2006) Increased risk of myocardial infarction as first manifestation of ischaemic heart disease and nonselective nonsteroidal anti-inflammatory drugs. Br J Clin Pharmacol 61(6):730–737PubMedGoogle Scholar
  101. 101.
    Weir MR, Sperling RS, Reicin A, Gertz BJ (2003) Selective Cox-2 inhibition and cardiovascular effects: a review of the rofecoxib development program. Am Heart J 146:591–604PubMedGoogle Scholar
  102. 102.
    Kang DW, Choi KY, Min DS (2011) Phospholipase D meets wnt signaling: a new target for cancer therapy. Cancer Res 71(2):293–297PubMedGoogle Scholar
  103. 103.
    Barker N et al (2009) Crypt stem cells as the cells-of-origin of intestinal cancer. Nature 457:608–611PubMedGoogle Scholar
  104. 104.
    Sangiorgi E, Capecchi MR (2008) Bmi1 is expressed in vivo in intestinal stem cells. Nat Genet 40:915–920PubMedGoogle Scholar
  105. 105.
    Li L, Clevers H (2010) Coexistence of quiescent and active adult stem cells in mammals. Science 327:542–545PubMedGoogle Scholar
  106. 106.
    Hara A, Yoshimi N, Niwa M, Ino N, Mori H (1997) Apoptosis induced by NS-398, a selective cyclooxygenase-2 inhibitor, in human colorectal cancer cell lines. Jpn J Cancer Res 88(6):600–604PubMedGoogle Scholar
  107. 107.
    Martin S, Phillips DC, Szekely-Szucs K, Elghazi L, Desmots F, Houghton JA (2005) Cyclooxygenase-2 inhibition sensitizes human colon carcinoma cells to TRAIL-induced apoptosis through clustering of DR5 and concentrating death-inducing signaling complex components into ceramide-enriched caveolae. Cancer Res 65(24):11447–11458PubMedGoogle Scholar
  108. 108.
    Zhang L, Yu J, Park BH, Kinzler KW, Vogelstein B (2000) Role of BAX in apoptotic response to anticancer agents. Science 290:989–992PubMedGoogle Scholar
  109. 109.
    Qui W, Wang X, Leibowitz B, Liu H, Barker N, Okada H et al (2010) Chemoprevention by nonsteroidal anti-inflammatory drugs eliminates oncogenic intestinal stem cells via SMAC-dependent apoptosis. Proc Natl Acad Sci USA 107(46):20027–20032Google Scholar
  110. 110.
    Cianchi F, Cortesini C, Bechi P, Fantappie O, Messerini L, Vannacci A et al (2001) Up-regulation of cyclooxygenase-2 gene expression correlates with tumor angiogenesis in human colorectal cancer. Gastroenterology 121(6):1339–1347PubMedGoogle Scholar
  111. 111.
    Williams CS, Tsujii M, Reese J, Dey SK, DuBois RN (2000) Host cyclooxygenase-2 modulates carcinoma growth. J Clin Invest 105(11):1589–1594PubMedGoogle Scholar
  112. 112.
    Dormond O, Foletti A, Paroz C, Ruegg C (2001) NSAIDs inhibit alpha V beta 3 integrin-mediated and Cdc42/Rac-dependent endothelial-cell spreading, migration and angiogenesis. Nat Med 7(9):1041–1047PubMedGoogle Scholar
  113. 113.
    Masferrer JL, Leahy KM, Koki AT, Zweifel BS, Settle SL, Woerner BM et al (2000) Antiangiogenic and antitumor activities of cyclooxygenase-2 inhibitors. Cancer Res 60(5):1306–1311PubMedGoogle Scholar
  114. 114.
    Shao J, Lee SB, Guo H et al (2003) Prostaglandin E2 stimulates the growth of colon cancer cells via induction of amphiregulin. Cancer Res 63:5218–5223PubMedGoogle Scholar
  115. 115.
    Moran AE, Hunt DH, Javid SH, Redston M, Carothers AM, Bertagnolli MM (2004) Apc deficiency is associated with increased Egfr activity in the intestinal enterocytes and adenomas of C57BL/6J-Min/+ mice. J Biol Chem 279(41):43261–43272PubMedGoogle Scholar
  116. 116.
    Hsu AL, Ching TT, Wang DS, Song X, Rangnekar VM, Chen CS (2000) The cyclooxygenase-2 inhibitor celecoxib induces apoptosis by blocking Akt activation in human prostate cancer cells independently of Bcl-2. J Biol Chem 275(15):11397–11403PubMedGoogle Scholar
  117. 117.
    Carothers AM, Javid SH, Moran AE, Hunt DM, Redston M, Bertagnolli MM (2006) Deficient E-cadherin adhesion in C57BL/6J-Min/+ mice is associated with increased tyrosine kinase activity and RhoA-dependent actomyosin contractility. Exp Cell Res 312:387–400PubMedGoogle Scholar
  118. 118.
    Sertznig P, Seifert M, Tilgen W, Reichrath J (2007) Prevent concepts and future outlook: function of perixosome proliferator-activated receptors (PPARs) for pathogenesis, progression, and therapy of cancer. J Cell Physiol 212:1–12PubMedGoogle Scholar
  119. 119.
    He TC, Chan TA, Vogelstein B, Kinzler KW (1999) PPARdelta is an APC-regulated target of nonsteroidal anti-inflammatory drugs. Cell 99(3):335–345PubMedGoogle Scholar
  120. 120.
    Goppelt-Struebe M (1997) Molecular mechanisms involved in the regulation of prostaglandin biosynthesis by glucocorticoids. Biochem Pharmacol 53(10):1389–1395PubMedGoogle Scholar
  121. 121.
    Yamamoto Y, Yin MJ, Lin KM, Gaynor RB (1999) Sulindac inhibits activation of the NF-kappaB pathway. J Biol Chem 274(38):27307–27314PubMedGoogle Scholar
  122. 122.
    Kune GA, Kune S, Watson LF (1988) Colorectal cancer risk, chronic illnesses, operations, and medications: case control results from the Melbourne Colorectal Cancer Study. Cancer Res 48(15):4399–4404PubMedGoogle Scholar
  123. 123.
    Thun MJ, Namboodiri MM, Calle EE, Flanders WD, Heath CW Jr (1993) Aspirin use and risk of fatal cancer. Cancer Res 53(6):1322–1327PubMedGoogle Scholar
  124. 124.
    Yao R, Rioux N, Castonguay A, You M (2000) Inhibition of COX-2 and induction of apoptosis: two determinants of nonsteroidal anti-inflammatory drugs’ chemopreventive efficacies in mouse lung tumorigenesis. Exp Lung Res 26(8):731–742PubMedGoogle Scholar
  125. 125.
    Rothwell PA, Wilson M, Elwin CE, Norrving B, Algra A, Warlow CP et al (2011) Long-term effect of aspirin on colorectal cancer incidence and mortality: 2-year follow-up of five randomized trials. Lancet 376:1741–1750Google Scholar
  126. 126.
    Johnson CC, Hayes RB, Schoen RE, Gunter MJ, Huang WY (2010) Non-steroidal anti-inflammatory drug use and colorectal polyps in the prostate, lung, colorectal, and ovarian cancer screening trial. Am J Gastroenterol 105:2646–2655PubMedGoogle Scholar
  127. 127.
    van Stolk R, Stoner G, Hayton WL, Chan K, DeYoung B, Kresty L et al (2000) Phase I trial of exisulind (sulindac sulfone, FGN-1) as a chemopreventive agent in patients with familial adenomatous polyposis. Clin Cancer Res 6(1):78–89PubMedGoogle Scholar
  128. 128.
    Hirota C, Iida M, Aoyagi K, Matsumoto T, Tada S, Yao T et al (1996) Effect of indomethacin suppositories on rectal polyposis in patients with familial adenomatous polyposis. Cancer 78(8):1660–1665PubMedGoogle Scholar
  129. 129.
    Steinbach G, Lynch PM, Phillips RK, Wallace MH, Hawk E, Gordon GB et al (2000) The effect of celecoxib, a cyclooxygenase-2 inhibitor, in familial adenomatous polyposis. N Engl J Med 342(26):1946–1952PubMedGoogle Scholar
  130. 130.
    Sandler RS, Halabi S, Baron JA, Budinger S, Paskett E, Keresztes R et al (2003) A randomized trial of aspirin to prevent colorectal adenomas in patients with previous colorectal cancer. N Engl J Med 348(10):1939Google Scholar
  131. 131.
    Benamouzig R, Deyra J, Martin A, Mejou B, Raynaud J-J, Girard B, et al (2006) Daily soluble aspirin and prevention of colorectal adenoma recurrence: four years results of the APACC trial. American Gastroenterological Society Annual Meeting Abstracts. Gastroenterology 130(A101):869Google Scholar
  132. 132.
    Logan RE, Muir KR, Grainge MJ, Armitage NC, Shepherd VC, Group UT (2006) Aspirin for the prevention of recurrent colorectal adenomas – results of the UKCAP trial. American Gastroenterological Society Meeting Abstracts. Gastroenterology 130(A64):438Google Scholar
  133. 133.
    Bresalier RS, Sandler RS, Quan H, Bolognese JA, Oxenius B, Horgan K et al (2005) Cardiovascular events associated with rofecoxib in a colorectal adenoma chemoprevention trial. N Engl J Med 352(11):1092–1102PubMedGoogle Scholar
  134. 134.
    Baron JA, Sandler RS, Bresalier RS, Quan H, Riddell R, Lanas A et al (2006) A randomized trial of rofecoxib for the chemoprevention of colorectal adenomas. Gastroenterology 131(6):1674–1682PubMedGoogle Scholar
  135. 135.
    Chan AT, Ogino S, Fuchs CS (2009) Aspirin use and survival after diagnosis of colorectal cancer. JAMA 302:649–658PubMedGoogle Scholar
  136. 136.
    Chan AT, Ogino S, Fuchs CS (2007) Aspirin and the risk of colorectal cancer in relation to the expression of COX-2. N Eng J Med 356:2131–2142Google Scholar
  137. 137.
    Teicher BA, Korbut TT, Meon K et al (1994) Cyclooxygenase and lipoxygenase inhibitors as modulators of cancer therapies. Cancer Chemother Pharmacol 33:515–522PubMedGoogle Scholar
  138. 138.
    Pyo H, Choy H, Amorino GP et al (2001) A selective cyclooxygenase-2 inhibitor, NS-398, enhances the effect of radiation in vitro and in vivo preferentially on the cells that express cyclooxygenase-2. Clin Cancer Res 7:2998–3005PubMedGoogle Scholar
  139. 139.
    Kishi K, Petersen S, Petersen C et al (2000) Preferential enhancement of tumor radioresponse by a cyclooxygenase-2 inhibitor. Cancer Res 60:1326–1331PubMedGoogle Scholar
  140. 140.
    Ferrandina G, Lauriola D, DiStefano MG (2002) Increased cyclooxygenase-2 expression is associated with chemotherapy resistance and poor survival in cervical cancer patients. J Clin Oncol 20:973–981PubMedGoogle Scholar
  141. 141.
    Altorki NK, Port JL, Zhang F, Golijanin D, Thaler HT, Duffield-Lillico AJ et al (2005) Chemotherapy induces the expression of cyclooxygenase-2 in non-small cell lung cancer. Clin Cancer Res 11:114191–114197Google Scholar
  142. 142.
    Ferrandina G, Lauriola L, Zannoni GF et al (2002) Increased cyclooxygenase-2 (COX-2) expression is associated with chemotherapy resistance and outcome in ovarian cancer patients. Ann Oncol 13:1205–1211PubMedGoogle Scholar
  143. 143.
    Uchida K, Schneider S, Yochim JM, Kuramochi H, Hayashi K, Takasaki K et al (2005) Intratumoral COX-2 gene expression is a predictive factor for colorectal cancer response to fluoropyrimidine-based chemotherapy. Clin Cancer Res 11(9):3363–3368PubMedGoogle Scholar
  144. 144.
    Edelman MJ, Watson D, Wang X, Morrison C, Kratzke RA, Jewell S et al (2008) Eicosanoid modulation in advanced lung cancer: cyclooxygenase-2 expression is a positive predictive factor for celecoxib  +  chemotherapy – Cancer and Leukemia Group B Trial 30203. J Clin Oncol 26(6):848–855PubMedGoogle Scholar
  145. 145.
    Ratnasinghe D, Daschner PJ, Anver MR et al (2001) Cyclooxygenase-2 P-glycoprotein-170 and drug resistance: is chemoprevention against multidrug resistance possible? Anticancer Res 21:2141–2147PubMedGoogle Scholar
  146. 146.
    Raspollini MR, Amunni G, Villanucci A, Boddi V, Taddei GL (2006) Cox-2 and preoperative CA-125 level are strongly correlated with survival and clinical responsiveness to chemotherapy in ovarian cancer. Acta Obstet Gynecol Scand 85(4):493–498PubMedGoogle Scholar
  147. 147.
    Subbaramaiah K, Hart JC, Norton L, Dannenberg AJ (2000) Microtubule-interfering agents stimulate the transcription of cyclooxygenase-2. Evidence for involvement of ERK1/2 and p38 mitogen-activated protein kinase pathways. J Biol Chem 275:14838–14845PubMedGoogle Scholar
  148. 148.
    Lundholm K, Gelin J, Hyltander A, Lonnroth C, Sandstrom R, Svaninger G et al (1994) Anti-inflammatory treatment may prolong survival in undernourished patients with metastatic solid tumors. Cancer Res 54(21):5602–5606PubMedGoogle Scholar
  149. 149.
    Altorki NK, Keresztes RS, Port JL et al (2003) Celecoxib, a selective cyclooxygenase-2 inhibitor, enhances the response to preoperative paclitaxel/carboplatin in early-stage non-small cell lung cancer. J Clin Oncol 21:2645–2650PubMedGoogle Scholar
  150. 150.
    Chow LW, Loo WT, Wai CC, Lui EL, Zhu L, Toi M (2005) Study of Cox-2, Ki67, and p53 expression to predict effectiveness of 5-fluorouracil, epirubicin and cyclophosphamide with celecoxib in treatment of breast cancer patients. Biomed Pharmacother 59(Suppl 2):S298–S301PubMedGoogle Scholar
  151. 151.
    Chow LW, Wong JL, Toi ML (2003) Celecoxib anti-aromatase neoadjuvant trial for locally advanced breast cancer: preliminary report. J Steroid Biochem Mol Biol 86:443–447PubMedGoogle Scholar
  152. 152.
    Milella M, Gelibter A, DiCosimo S, Bria E, Ruggieri EM, Carlini P et al (2004) Pilot study of celecoxib and infusional 5-fluorouracil as second-line treatment for advanced pancreatic carcinoma. Cancer 101(1):133–138PubMedGoogle Scholar
  153. 153.
    Govindan R, McLeod H, Mantravadi P, Fineberg N, Helft P, Kesler K et al (2004) Cisplatin, fluorouracil, celecoxib, and RT in resectable esophageal cancer: preliminary results. Oncology 14(Suppl 14):18–21Google Scholar
  154. 154.
    Mrozek E, Kloos RT, Ringel MD, Kresty L, Snider P, Arbogast D et al (2006) Phase II study of celecoxib in metastatic differentiated thyroid carcinoma. J Clin Endocrinol Metab 91(6):2201–2204PubMedGoogle Scholar
  155. 155.
    Prince HM, Mileshkin L, Roberts A, Ganju V, Underhill C, Catalano J et al (2005) A multicenter phase II trial of thalidomide and celecoxib for patients with relapsed and refractory multiple myeloma. Clin Cancer Res 11(15):5504–5514PubMedGoogle Scholar
  156. 156.
    Reardon DA, Quinn JA, Vredenburgh J, Rich JN, Gururangan S, Badruddoja M et al (2005) Phase II trial of irinotecan plus celecoxib in adults with recurrent malignant glioma. Cancer 103(2):329–338PubMedGoogle Scholar
  157. 157.
    Csiki I, Dang T, Gonzalez A, Gautam S, Sandler A, Campbell N et al (2002) Cyclooxygenase-2 inhibition  +  docetaxel in recurrent non-small cell lung cancer: preliminary results of a phase II trial (THO-0054). Proc Am Soc Clin Oncol 21:1187Google Scholar
  158. 158.
    Pan CX, Loehrer P, Seitz D, Helft P, Juliar B, Ansari R et al (2005) A phase II trial of irinotecan, 5-fluorouracil and leucovorin combined with celecoxib and glutamine as first-line therapy for advanced colorectal cancer. Oncology 69(1):63–70PubMedGoogle Scholar
  159. 159.
    Gasparini G, Gattuso D, Morabito A, Longo R, Torino F, Sarmiento R et al (2005) Combined therapy with weekly irinotecan, infusional 5-fluorouracil and the selective Cox-2 inhibitor rofecoxib is a safe and effective second-line treatment in metastatic colorectal cancer. Oncologist 10:710–717PubMedGoogle Scholar
  160. 160.
    Zhang L, Ren X, Alt E, Huang S, Xu Z, Lynch PM et al (2010) Chemoprevention of colorectal cancer by targeting APC-deficient cells for apoptosis. Nature 464(7291):1058–1061PubMedGoogle Scholar
  161. 161.
    Toyokuni T, Kumar JS, Walsh JC, Shapiro A, Talley JJ, Phelps ME et al (2005) Synthesis of 4-(5-[18F]fluoromethyl-3-phenylisoxazol-4-yl) benzene-sulfonamide, a new [18F]fluorinated analogue of valdecoxib, as a potential radiotracer for imaging cyclooxygenase-2 with positron emission tomography. Bioorg Med Chem Lett 15:4699–4702PubMedGoogle Scholar
  162. 162.
    Schuller HM, Kabalka G, Smith G, Mereddy A, Akula M, Cekanova M (2006) Detection of overexpressed COX-2 in precancerous lesions of hamster pancreas and lungs by molecular imaging: implications for early diagnosis and prevention. Chem Med Chem 1:603–610PubMedGoogle Scholar
  163. 163.
    de Vries EF, Doorduin J, Dierckx RA, van Waarde A (2008) Evaluation of [(11)C]rofecoxib as PET tracer for cyclooxygenase 2 overexpression in rat models of inflammation. Nucl Med Biol 35:35–42PubMedGoogle Scholar
  164. 164.
    Wuest F, Kniess T, Bergmann R, Pietzsch J (2008) Synthesis and evaluation in vitro and in vivo of a 11C-labeled cyclooxygenase-2 (COX-2) inhibitor. Bioorg Med Chem 16:7662–7670PubMedGoogle Scholar

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© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Division of Surgical OncologyDana Farber Cancer Institute, Brigham & Women’s Hospital, Harvard Medical SchoolBostonUSA

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