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Cyclooxygenase-2 and its role in colorectal cancer development

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Abstract

Cyclooxygenase 2 (COX-2), also called prostaglandin endoperoxide synthase 2, is involved in colorectal tumor development. This review deals with particular questions raised in this field such as the mechanisms of COX-2 related tumor promotion, the role of the different types of cells (epithelial and interstitial) expressing COX-2, the factors that trigger COX-2 induction, and the clinical potential of selective COX-2 inhibitors to treat or prevent colorectal tumors. Several mechanisms of COX-2 related tumor promotion have been identified. Some are dependent on prostaglandin E2 production (such as induction of cell proliferation, angiogenenis or local immunosuppression, inhibition of apoptosis, increase in cell motility) and others are not (such as carcinogen activation or malondialdehyde production). COX-2 expression has been demonstrated in epithelial cells of colorectal cancers and adenomas and also in interstitial cells. These cells correspond to macrophages and/or fibroblasts and endothelial cells. COX-2 expression in these interstitial cells participates in tumor development. Factors or events that trigger COX-2 expression include oncogene activation, antioncogene inactivation, cytokines, growth factors, some fatty acids, bile salts, and mucins. Finally, selective COX-2 inhibitors may be effective in preventing or treating colorectal adenomas or carcinomas. However, their real efficiency and the cost/benefit balance are currently evaluated, and no definite conclusion can be made at the moment.

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References

  1. Aaltonen LA, Peltomaki P, Mecklin JP, Jarvinen H, Jass JR, Green JS, Lynch HT, Watson P, Tallqvist G, Juhola M et al. (1994) Replication errors in benign and malignant tumors from hereditary nonpolyposis colorectal cancer patients. Cancer Res 54:1645–1648

    CAS  PubMed  Google Scholar 

  2. Araki Y, Okamura S, Hussain SP, Nagashima M, He P, Shiseki M, Miura K, Harris CC (2003) Regulation of cyclooxygenase-2 expression by the Wnt and ras pathways. Cancer Res 63:728–734

    CAS  PubMed  Google Scholar 

  3. Arvind P, Papavassiliou ED, Tsioulias GJ, Qiao L, Lovelace CI, Duceman B, Rigas B (1995) Prostaglandin E2 down-regulates the expression of HLA-DR antigen in human colon adenocarcinoma cell lines. Biochemistry 34:5604–5609

    Google Scholar 

  4. Bamba H, Ota S, Kato A, Adachi A, Itoyama S, Matsuzaki F (1999) High expression of cyclooxygenase-2 in macrophages of human colonic adenoma. Int J Cancer 83:470–475

    Article  CAS  PubMed  Google Scholar 

  5. Becerra CR, Frenkel EP, Ashfaq R, Gaynor RB (2003) Increased toxicity and lack of efficacy of Rofecoxib in combination with chemotherapy for treatment of metastatic colorectal cancer: a phase II study. Int J Cancer 105:868–872

    Article  CAS  PubMed  Google Scholar 

  6. Benamouzig R, Deyra J, Martin A, Girard B, Jullian E, Piednoir B, Couturier D, Coste T, Little J, Chaussade S (2003) Daily soluble aspirin and prevention of colorectal adenoma recurrence: one-year results of the APACC trial. Gastroenterology 125:328–336

    Article  CAS  PubMed  Google Scholar 

  7. Cao Y, Pearman AT, Zimmerman GA, McIntyre TM, Prescott SM (2000) Intracellular unesterified arachidonic acid signals apoptosis. Proc Natl Acad Sci U S A 97:11280–11285

    Article  CAS  PubMed  Google Scholar 

  8. Chan TA, Morin PJ, Vogelstein B, Kinzler KW (1998) Mechanisms underlying nonsteroidal antiinflammatory drug-mediated apoptosis. Proc Natl Acad Sci U S A 95:681–686

    Article  CAS  PubMed  Google Scholar 

  9. Chandrasekharan NV, Dai H, Roos KL, Evanson NK, Tomsik J, Elton TS, Simmons DL (2002) COX-3, a cyclooxygenase-1 variant inhibited by acetaminophen and other analgesic/antipyretic drugs: cloning, structure, and expression. Proc Natl Acad Sci U S A 99:13926–13931. Epub 12002 Sep 13919

    Article  CAS  PubMed  Google Scholar 

  10. Chapple KS, Cartwright EJ, Hawcroft G, Tisbury A, Bonifer C, Scott N, Windsor AC, Guillou PJ, Markham AF, Coletta PL, Hull MA (2000) Localization of cyclooxygenase-2 in human sporadic colorectal adenomas. Am J Pathol 156:545–553

    CAS  PubMed  Google Scholar 

  11. Chulada PC, Thompson MB, Mahler JF, Doyle CM, Gaul BW, Lee C, Tiano HF, Morham SG, Smithies O, Langenbach R (2000) Genetic disruption of Ptgs-1, as well as Ptgs-2, reduces intestinal tumorigenesis in Min mice. Cancer Res 60:4705–4708

    CAS  PubMed  Google Scholar 

  12. Cianchi F, Cortesini C, Bechi P, Fantappie O, Messerini L, Vannacci A, Sardi I, Baroni G, Boddi V, Mazzanti R, Masini E (2001) Up-regulation of cyclooxygenase 2 gene expression correlates with tumor angiogenesis in human colorectal cancer. Gastroenterology 121:1339–1347

    CAS  PubMed  Google Scholar 

  13. Daniel TO, Liu H, Morrow JD, Crews BC, Marnett LJ (1999) Thromboxane A2 is a mediator of cyclooxygenase-2-dependent endothelial migration and angiogenesis. Cancer Res 59:4574–4577

    CAS  PubMed  Google Scholar 

  14. Deviere J (2002) Do selective cyclo-oxygenase inhibitors eliminate the adverse events associated with nonsteroidal anti-inflammatory drug therapy? Eur J Gastroenterol Hepatol 14:S29–S33

    CAS  PubMed  Google Scholar 

  15. Dinchuk JE, Car BD, Focht RJ, Johnston JJ, Jaffee BD, Covington MB, Contel NR, Eng VM, Collins RJ, Czerniak PM et al. (1995) Renal abnormalities and an altered inflammatory response in mice lacking cyclooxygenase II. Nature 378:406–409

    Article  CAS  PubMed  Google Scholar 

  16. Dixon DA, Tolley ND, King PH, Nabors LB, McIntyre TM, Zimmerman GA, Prescott SM (2001) Altered expression of the mRNA stability factor HuR promotes cyclooxygenase-2 expression in colon cancer cells. J Clin Invest 108:1657–1665

    Article  CAS  PubMed  Google Scholar 

  17. 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 107:1183–1188

    CAS  PubMed  Google Scholar 

  18. Einspahr JG, Krouse RS, Yochim JM, Danenberg PV, Danenberg KD, Bhattacharyya AK, Martinez ME, Alberts DS (2003) Association between Cyclooxygenase expression and colorectal adenoma characteristics. Cancer Res 63:3891–3893

    CAS  PubMed  Google Scholar 

  19. Elder DJ, Baker JA, Banu NA, Moorghen M, Paraskeva C (2002) Human colorectal adenomas demonstrate a size-dependent increase in epithelial cyclooxygenase-2 expression. J Pathol 198:428–434

    Article  CAS  PubMed  Google Scholar 

  20. Elder DJ, Halton DE, Crew TE, Paraskeva C (2000) Apoptosis induction and cyclooxygenase-2 regulation in human colorectal adenoma and carcinoma cell lines by the cyclooxygenase-2-selective non-steroidal anti-inflammatory drug NS-398. Int J Cancer 86:553–560

    Article  CAS  PubMed  Google Scholar 

  21. Fenwick SW, Toogood GJ, Lodge JP, Hull MA (2003) The effect of the selective cyclooxygenase-2 inhibitor rofecoxib on human colorectal cancer liver metastases. Gastroenterology 125:716–729

    Article  CAS  PubMed  Google Scholar 

  22. Gallo O, Schiavone N, Papucci L, Sardi I, Magnelli L, Franchi A, Masini E, Capaccioli S (2003) Down-regulation of nitric oxide synthase-2 and cyclooxygenase-2 pathways by p53 in squamous cell carcinoma. Am J Pathol 163:723–732

    CAS  PubMed  Google Scholar 

  23. Giardiello FM, Hamilton SR, Krush AJ, Piantadosi S, Hylind LM, Celano P, Booker SV, Robinson CR, Offerhaus GJ (1993) Treatment of colonic and rectal adenomas with sulindac in familial adenomatous polyposis. N Engl J Med 328:1313–1316

    Article  CAS  PubMed  Google Scholar 

  24. Giovannucci E, Egan KM, Hunter DJ, Stampfer MJ, Colditz GA, Willett WC, Speizer FE (1995) Aspirin and the risk of colorectal cancer in women. N Engl J Med 333:609–614

    Article  CAS  PubMed  Google Scholar 

  25. 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 121:241–246

    CAS  PubMed  Google Scholar 

  26. Glinghammar B, Rafter J (2001) Colonic luminal contents induce cyclooxygenase 2 transcription in human colon carcinoma cells. Gastroenterology 120:401–410

    CAS  PubMed  Google Scholar 

  27. Gomez Cerezo J, Lubomirov Hristov R, Carcas Sansuan AJ, Vazquez Rodriguez JJ (2003) Outcome trials of COX-2 selective inhibitors: global safety evaluation does not promise benefits. Eur J Clin Pharmacol 59:169–175

    PubMed  Google Scholar 

  28. d’Halluin PN, Turlin B, Polard E, Dinasquet M, Pagenault M, Rioux N, Gosselin M, Bretagne JF, Heresbach D (2003) [Selective COX-2 inhibitor-associated colitis: two case reports]. Gastroenterol Clin Biol 27:932–935

    PubMed  Google Scholar 

  29. Hanif R, Pittas A, Feng Y, Koutsos MI, Qiao L, Staiano-Coico L, Shiff SI, Rigas B (1996) Effects of nonsteroidal anti-inflammatory drugs on proliferation and on induction of apoptosis in colon cancer cells by a prostaglandin-independent pathway. Biochem Pharmacol 52:237–245

    Article  CAS  PubMed  Google Scholar 

  30. Hao X, Bishop AE, Wallace M, Wang H, Willcocks TC, Maclouf J, Polak JM, Knight S, Talbot IC (1999) Early expression of cyclo-oxygenase-2 during sporadic colorectal carcinogenesis. J Pathol 187:295–301

    Article  CAS  PubMed  Google Scholar 

  31. Hasegawa K, Ichikawa W, Fujita T, Ohno R, Okusa T, Yoshinaga K, Sugihara K (2001) Expression of cyclooxygenase-2 (COX-2) mRNA in human colorectal adenomas. Eur J Cancer 37:1469–1474

    Article  CAS  PubMed  Google Scholar 

  32. Hull MA, Booth JK, Tisbury A, Scott N, Bonifer C, Markham AF, Coletta PL (1999) Cyclooxygenase 2 is up-regulated and localized to macrophages in the intestine of Min mice. Br J Cancer 79:1399–1405

    Article  CAS  PubMed  Google Scholar 

  33. Inaba T, Sano H, Kawahito Y, Hla T, Akita K, Toda M, Yamashina I, Inoue M, Nakada H (2003) Induction of cyclooxygenase-2 in monocyte/macrophage by mucins secreted from colon cancer cells. Proc Natl Acad Sci U S A 100:2736–2741. Epub 2003 Feb 2721

    Article  CAS  PubMed  Google Scholar 

  34. Jacoby RF, Seibert K, Cole CE, Kelloff G, Lubet RA (2000) The cyclooxygenase-2 inhibitor celecoxib is a potent preventive and therapeutic agent in the min mouse model of adenomatous polyposis. Cancer Res 60:5040–5044

    CAS  PubMed  Google Scholar 

  35. Jones DA, Carlton DP, McIntyre TM, Zimmerman GA, Prescott SM (1993) Molecular cloning of human prostaglandin endoperoxide synthase type II and demonstration of expression in response to cytokines. J Biol Chem 268:9049–9054

    CAS  PubMed  Google Scholar 

  36. Karnes WE Jr, Shattuck-Brandt R, Burgart LJ, DuBois RN, Tester DJ, Cunningham JM, Kim CY, McDonnell SK, Schaid DJ, Thibodeau SN (1998) Reduced COX-2 protein in colorectal cancer with defective mismatch repair. Cancer Res 58:5473–5477

    CAS  PubMed  Google Scholar 

  37. Kawamori T, Rao CV, Seibert K, Reddy BS (1998) Chemopreventive activity of celecoxib, a specific cyclooxygenase-2 inhibitor, against colon carcinogenesis. Cancer Res 58:409–412

    CAS  PubMed  Google Scholar 

  38. Kojima M, Morisaki T, Uchiyama A, Doi F, Mibu R, Katano M, Tanaka M (2001) Association of enhanced cyclooxygenase-2 expression with possible local immunosuppression in human colorectal carcinomas. Ann Surg Oncol 8:458–465

    Article  CAS  PubMed  Google Scholar 

  39. Lim H, Paria BC, Das SK, Dinchuk JE, Langenbach R, Trzaskos JM, Dey SK (1997) Multiple female reproductive failures in cyclooxygenase 2-deficient mice. Cell 91:197–208

    Article  CAS  PubMed  Google Scholar 

  40. Lin E, Morris JS, Ayers GD (2002) Effect of celecoxib on capecitabine-induced hand-foot syndrome and antitumor activity. Oncology (Huntingt) 16:31–37

    Google Scholar 

  41. Meade EA, McIntyre TM, Zimmerman GA, Prescott SM (1999) Peroxisome proliferators enhance cyclooxygenase-2 expression in epithelial cells. J Biol Chem 274:8328–8334

    Article  CAS  PubMed  Google Scholar 

  42. Morham SG, Langenbach R, Loftin CD, Tiano HF, Vouloumanos N, Jennette JC, Mahler JF, Kluckman KD, Ledford A, Lee CA et al. (1995) Prostaglandin synthase 2 gene disruption causes severe renal pathology in the mouse. Cell 83:473–482

    Article  CAS  PubMed  Google Scholar 

  43. Oshima M, Dinchuk JE, Kargman SL, Oshima H, Hancock B, Kwong E, Trzaskos JM, Evans JF, Taketo MM (1996) Suppression of intestinal polyposis in Apc delta716 knockout mice by inhibition of cyclooxygenase 2 (COX-2). Cell 87:803–809

    Article  CAS  PubMed  Google Scholar 

  44. Oshima M, Murai N, Kargman S, Arguello M, Luk P, Kwong E, Taketo MM, Evans JF (2001) Chemoprevention of intestinal polyposis in the Apcdelta716 mouse by rofecoxib, a specific cyclooxygenase-2 inhibitor. Cancer Res 61:1733–1740

    CAS  PubMed  Google Scholar 

  45. Pai R, Soreghan 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 8:289–293

    Article  CAS  PubMed  Google Scholar 

  46. Phillips RK, Wallace MH, Lynch PM, Hawk E, Gordon GB, Saunders BP, Wakabayashi N, Shen Y, Zimmerman S, Godio L, Rodrigues-Bigas M, Su LK, Sherman J, Kelloff G, Levin B, Steinbach G (2002) A randomised, double blind, placebo controlled study of celecoxib, a selective cyclooxygenase 2 inhibitor, on duodenal polyposis in familial adenomatous polyposis. Gut 50:857–860

    Article  CAS  PubMed  Google Scholar 

  47. Piazza GA, Alberts DS, Hixson LJ, Paranka NS, Li H, Finn T, Bogert C, Guillen JM, Brendel K, Gross PH, Sperl G, Ritchie J, Burt RW, Ellsworth L, Ahnen DJ, Pamukcu R (1997) Sulindac sulfone inhibits azoxymethane-induced colon carcinogenesis in rats without reducing prostaglandin levels. Cancer Res 57:2909–2915

    CAS  PubMed  Google Scholar 

  48. Prescott SM, White RL (1996) Self-promotion? Intimate connections between APC and prostaglandin H synthase-2. Cell 87:783–786

    Article  CAS  PubMed  Google Scholar 

  49. Rao M, Yang W, Seifalian AM, Winslet MC (2004) Role of cyclooxygenase-2 in the angiogenesis of colorectal cancer. Int J Colorectal Dis 19:1–11

    Google Scholar 

  50. Rigas B, Goldman IS, Levine L (1993) Altered eicosanoid levels in human colon cancer. J Lab Clin Med 122:518–523

    CAS  PubMed  Google Scholar 

  51. Sandler RS, Halabi S, Baron JA, Budinger S, Paskett E, Keresztes R, Petrelli N, Pipas JM, Karp DD, Loprinzi CL, Steinbach G, Schilsky R (2003) A randomized trial of aspirin to prevent colorectal adenomas in patients with previous colorectal cancer. N Engl J Med 348:883–890

    Article  CAS  PubMed  Google Scholar 

  52. Sano H, Kawahito Y, Wilder RL, Hashiramoto A, Mukai S, Asai K, Kimura S, Kato H, Kondo M, Hla T (1995) Expression of cyclooxygenase-1 and -2 in human colorectal cancer. Cancer Res 55:3785–3789

    CAS  PubMed  Google Scholar 

  53. Seno H, Oshima M, Ishikawa TO, Oshima H, Takaku K, Chiba T, Narumiya S, Taketo MM (2002) Cyclooxygenase 2- and prostaglandin E (2) receptor EP (2)-dependent angiogenesis in Apc (Delta716) mouse intestinal polyps. Cancer Res 62:506–511

    CAS  PubMed  Google Scholar 

  54. Shao J, Sheng H, Inoue H, Morrow JD, DuBois RN (2000) Regulation of constitutive cyclooxygenase-2 expression in colon carcinoma cells. J Biol Chem 275:33951–33956

    Article  CAS  PubMed  Google Scholar 

  55. Shattuck-Brandt RL, Varilek GW, Radhika A, Yang F, Washington MK, DuBois RN (2000) Cyclooxygenase 2 expression is increased in the stroma of colon carcinomas from IL-10 (-/-) mice. Gastroenterology 118:337–345

    CAS  PubMed  Google Scholar 

  56. Sheng H, Shao J, Hooton EB, Tsujii M, DuBois RN, Beauchamp RD (1997) Cyclooxygenase-2 induction and transforming growth factor beta growth inhibition in rat intestinal epithelial cells. Cell Growth Differ 8:463–470

    CAS  PubMed  Google Scholar 

  57. 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 58:362–366

    CAS  PubMed  Google Scholar 

  58. Sheng H, Shao J, Dubois RN (2001) K-Ras-mediated increase in cyclooxygenase 2 mRNA stability involves activation of the protein kinase B1. Cancer Res 61:2670–2675

    CAS  PubMed  Google Scholar 

  59. Sheng H, Shao J, Washington MK, DuBois RN (2001) Prostaglandin E2 increases growth and motility of colorectal carcinoma cells. J Biol Chem 276:18075–18081

    Article  CAS  PubMed  Google Scholar 

  60. Shiff SJ, Rigas B (1997) Nonsteroidal anti-inflammatory drugs and colorectal cancer: evolving concepts of their chemopreventive actions. Gastroenterology 113:1992–1998

    CAS  PubMed  Google Scholar 

  61. Silverstein FE, Faich G, Goldstein JL, Simon LS, Pincus T, Whelton A, Makuch R, Eisen G, Agrawal NM, Stenson WF, Burr AM, Zhao WW, Kent JD, Lefkowith JB, Verburg KM, Geis GS (2000) Gastrointestinal toxicity with celecoxib vs nonsteroidal anti-inflammatory drugs for osteoarthritis and rheumatoid arthritis: the CLASS study: a randomized controlled trial. Celecoxib Long-term Arthritis Safety Study. JAMA 284:1247–1255

    Article  CAS  PubMed  Google Scholar 

  62. Sinicrope FA, Lemoine M, Xi L, Lynch PM, Cleary KR, Shen Y, Frazier ML (1999) Reduced expression of cyclooxygenase 2 proteins in hereditary nonpolyposis colorectal cancers relative to sporadic cancers. Gastroenterology 117:350–358

    CAS  PubMed  Google Scholar 

  63. Smith WL, Garavito RM, DeWitt DL (1996) Prostaglandin endoperoxide H synthases (cyclooxygenases)-1 and -2. J Biol Chem 271:33157–33160

    Article  CAS  PubMed  Google Scholar 

  64. Smith WL, DeWitt DL, Garavito RM (2000) Cyclooxygenases: structural, cellular, and molecular biology. Annu Rev Biochem 69:145–182

    Article  CAS  PubMed  Google Scholar 

  65. Sonoshita M, Takaku K, Oshima M, Sugihara K, Taketo MM (2002) Cyclooxygenase-2 expression in fibroblasts and endothelial cells of intestinal polyps. Cancer Res 62:6846–6849

    CAS  PubMed  Google Scholar 

  66. Steinbach G, Lynch PM, Phillips RK, Wallace MH, Hawk E, Gordon GB, Wakabayashi N, Saunders B, Shen Y, Fujimura T, Su LK, Levin B (2000) The effect of celecoxib, a cyclooxygenase-2 inhibitor, in familial adenomatous polyposis. N Engl J Med 342:1946–1952

    Article  CAS  PubMed  Google Scholar 

  67. Subbaramaiah K, Altorki N, Chung WJ, Mestre JR, Sampat A, Dannenberg AJ (1999) Inhibition of cyclooxygenase-2 gene expression by p53. J Biol Chem 274:10911–10915

    Article  CAS  PubMed  Google Scholar 

  68. Thun MJ, Henley SJ, Patrono C (2002) Nonsteroidal anti-inflammatory drugs as anticancer agents: mechanistic, pharmacologic, and clinical issues. J Natl Cancer Inst 94:252–266

    Article  CAS  PubMed  Google Scholar 

  69. Tiano HF, Loftin CD, Akunda J, Lee CA, Spalding J, Sessoms A, Dunson DB, Rogan EG, Morham SG, Smart RC, Langenbach R (2002) Deficiency of Either Cyclooxygenase (COX)-1 or COX-2 Alters Epidermal Differentiation and Reduces Mouse Skin Tumorigenesis. Cancer Res 62:3395–3401

    CAS  PubMed  Google Scholar 

  70. Tomozawa S, Nagawa H, Tsuno N, Hatano K, Osada T, Kitayama J, Sunami E, Nita ME, Ishihara S, Yano H, Tsuruo T, Shibata Y, Muto T (1999) Inhibition of haematogenous metastasis of colon cancer in mice by a selective COX-2 inhibitor, JTE-522. Br J Cancer 81:1274–1279

    Article  CAS  PubMed  Google Scholar 

  71. Tsujii M, DuBois RN (1995) Alterations in cellular adhesion and apoptosis in epithelial cells overexpressing prostaglandin endoperoxide synthase 2. Cell 83:493–501

    Article  CAS  PubMed  Google Scholar 

  72. Tsujii M, Kawano S, DuBois RN (1997) Cyclooxygenase-2 expression in human colon cancer cells increases metastatic potential. Proc Natl Acad Sci U S A 94:3336–3340

    Article  CAS  PubMed  Google Scholar 

  73. Tsujii M, Kawano S, Tsuji S, Sawaoka H, Hori M, DuBois RN (1998) Cyclooxygenase regulates angiogenesis induced by colon cancer cells. Cell 93:705–716

    Article  CAS  PubMed  Google Scholar 

  74. Waddell WR, Ganser GF, Cerise EJ, Loughry RW (1989) Sulindac for polyposis of the colon. Am J Surg 157:175–179

    Article  CAS  PubMed  Google Scholar 

  75. Wallace JL, Bak A, McKnight W, Asfaha S, Sharkey KA, MacNaughton WK (1998) Cyclooxygenase 1 contributes to inflammatory responses in rats and mice: implications for gastrointestinal toxicity. Gastroenterology 115:101–109

    CAS  PubMed  Google Scholar 

  76. Wallace JL, Chapman K, McKnight W (1999) Limited anti-inflammatory efficacy of cyclo-oxygenase-2 inhibition in carrageenan-airpouch inflammation. Br J Pharmacol 126:1200–1204

    CAS  PubMed  Google Scholar 

  77. Wendum D, Boelle PY, Rigau V, Sebbagh N, Olschwang S, Mourra N, Parc R, Trugnan G, Masliah J, Flejou JF (2003) Mucinous colon carcinomas with microsatellite instability have a lower microvessel density and lower vascular endothelial growth factor expression. Virchows Arch 442:111–117

    CAS  PubMed  Google Scholar 

  78. Wendum D, Svrcek M, Rigau V, Boelle PY, Sebbagh N, Parc R, Masliah J, Trugnan G, Flejou JF (2003) COX-2, inflammatory secreted PLA2, and cytoplasmic PLA2 protein expression in small bowel adenocarcinomas compared with colorectal adenocarcinomas. Mod Pathol 16:130–136

    Article  PubMed  Google Scholar 

  79. Williams CS, Tsujii M, Reese J, Dey SK, DuBois RN (2000) Host cyclooxygenase-2 modulates carcinoma growth. J Clin Invest 105:1589–1594

    CAS  PubMed  Google Scholar 

  80. Yao M, Kargman S, Lam EC, Kelly CR, Zheng Y, Luk P, Kwong E, Evans JF, Wolfe MM (2003) Inhibition of cyclooxygenase-2 by rofecoxib attenuates the growth and metastatic potential of colorectal carcinoma in mice. Cancer Res 63:586–592

    CAS  PubMed  Google Scholar 

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  1. Service d’Anatomie Pathologique, Hôpital Saint-Antoine, AP-HP, 184 rue du Faubourg Saint-Antoine, 75571, Paris Cedex 12, France

    Dominique Wendum & Jean-François Fléjou

  2. Unité INSERM U538, Faculté de Médecine Saint-Antoine, Université Pierre et Marie Curie, 27 rue Chaligny, 75012, Paris, France

    Dominique Wendum, Joëlle Masliah & Germain Trugnan

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Correspondence to Dominique Wendum.

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Wendum, D., Masliah, J., Trugnan, G. et al. Cyclooxygenase-2 and its role in colorectal cancer development. Virchows Arch 445, 327–333 (2004). https://doi.org/10.1007/s00428-004-1105-2

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