1887
  1. Home
  2. A-Z Publications
  3. Avicenna
  4. Volume 2013, Issue 1
  5. Article
Volume 2013, Issue 1
  • EISSN: 2220-2749

Abstract

Prostaglandins, in particular prostaglandin E (PGE), are elevated in adenomas and colorectal cancers (CRC). Experimental and epidemiological studies have demonstrated reduced incidence of adenomas and CRC by inhibitors of prostanoid synthesis (NSAIDs). This study aimed to characterize the expression and localization of key enzymes/receptors for PGE synthesis in adenomas and CRC in comparison to normal colon. Immunoblotting and immunohistochemistry were used for semi-quantitative and qualitative analysis of COX-1, COX-2, mPGES-1 and the EP receptor in biopsies from patients undergoing resection of adenomas or surgery for CRC (Dukes' A-C). Normal colon served as control for the corresponding tumor in each of the CRC patients. COX-1 was decreased significantly in all groups of CRC (Dukes' A-C) compared to normal colon. In contrast, COX-2 was increased, but only in the combined group of CRC. Microsomal PGES-1 was increased in CRC (Duke's B), and EP was augmented in adenomas and CRC. The localization was predominantly epithelial in normal colon and in adenomas, while in CRC both epithelial- and stromal expression was demonstrated. The results support the PGE- pathway, with epithelial- stromal interactions, in the evolvement of adenomas and in the progression of CRC. Co-expression of COX-1 and COX-2 is in line with the preventive effects of non-specific NSAIDs on adenoma formation. The decrease of COX-1, in combination with an increase of COX-2, favors the potential use of selective COX-2 inhibitors as an adjunct therapy in CRC.

© 2013 Hedin, Rask, Zhu, Wickman, Wang, Brevinge, Thörn, Pontén, Sundfeldt, licensee Bloomsbury Qatar Foundation Journals.
Loading

Article metrics loading...

/content/journals/10.5339/avi.2013.5
2013-09-01
2024-12-22
Loading full text...

Full text loading...

/deliver/fulltext/avi/2013/1/avi.2013.5.html?itemId=/content/journals/10.5339/avi.2013.5&mimeType=html&fmt=ahah

References

  1. Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005; 55:2:74–108
     [Google Scholar]
  2. el-Akkad SM, Amer MH, Lin GS, Sabbah RS, Godwin JT. Pattern of cancer in Saudi Arabs referred to King Faisal Specialist Hospital. Cancer. 1986; 58:5:1172–1178
     [Google Scholar]
  3. Bener A, Moore MA, Ali R, El Ayoubi HR. Impacts of family history and lifestyle habits on colorectal cancer risk: a case-control study in Qatar. Asian Pac J Cancer Prev. 2010; 11:4:963–968
     [Google Scholar]
  4. Basaleem HO, Al-Sakkaf KA. Colorectal cancer among Yemeni patients. Characteristics and trends. Saudi Med J. 2004; 25:8:1002–1005
     [Google Scholar]
  5. Guraya SY, Eltinay OE. Higher prevalence in young population and rightward shift of colorectal carcinoma. Saudi Med J. 2006; 27:9:1391–1393
     [Google Scholar]
  6. Al-Kuraya KS, Bavi PP, Ezzat AA, Al-Dayel FA, Uddin S, Atizado VL, Al-Jomah NA, Amr SS, Sheikh SS, Sauter G, Simon R. Colorectal carcinoma from Saudi Arabia. Analysis of MLH-1, MSH-2 and p53 genes by immunohistochemistry and tissue microarray analysis. Saudi Med J. 2006; 27:3:323–328
     [Google Scholar]
  7. Jass JR. Hyperplastic polyps and colorectal cancer: is there a link? Clin Gastroenterol Hepatol. 2004; 2:1:1–8
     [Google Scholar]
  8. Wang D, Dubois RN. Prostaglandins and cancer. Gut. 2006; 55:1:115–122
     [Google Scholar]
  9. Chell S, Kaidi A, Williams AC, Paraskeva C. Mediators of PGE2 synthesis and signalling downstream of COX-2 represent potential targets for the prevention/treatment of colorectal cancer. Biochim Biophys Acta. 2006; 1766:1:104–119
     [Google Scholar]
  10. Kraus S, Arber N. Cancer: do aspirin and other NSAIDs protect against colorectal cancer? Nat Rev Gastroenterol Hepatol. 2011; 8:3:125–126
     [Google Scholar]
  11. Kargman SL, O'Neill GP, Vickers PJ, Evans JF, Mancini JA, Jothy S. Expression of prostaglandin G/H synthase-1 and -2 protein in human colon cancer. Cancer Res. 1995; 55:12:2556–2559
     [Google Scholar]
  12. Arber N, Eagle CJ, Spicak J, Rácz I, Dite P, Hajer J, Zavoral M, Lechuga MJ, Gerletti P, Tang J, Rosenstein RB, Macdonald K, Bhadra P, Fowler R, Wittes J, Zauber AG, Solomon SD, Levin B, PreSAP Trial Investigators . Celecoxib for the prevention of colorectal adenomatous polyps. N Engl J Med. 2006; 355:9:885–895
     [Google Scholar]
  13. Yoshimatsu K, Golijanin D, Paty PB, Soslow RA, Jakobsson PJ, DeLellis RA, Subbaramaiah K, Dannenberg AJ. Inducible microsomal prostaglandin E synthase is overexpressed in colorectal adenomas and cancer. Clin Cancer Res. 2001; 7:12:3971–3976
     [Google Scholar]
  14. Castellone MD, Teramoto H, Williams BO, Druey KM, Gutkind JS. Prostaglandin E2 promotes colon cancer cell growth through a Gs-axin-beta-catenin signaling axis. Science. 2005; 310:5753:1504–1510
     [Google Scholar]
  15. Levy DB, Smith KJ, Beazer-Barclay Y, Hamilton SR, Vogelstein B, Kinzler KW. Inactivation of both APC alleles in human and mouse tumors. Cancer Res. 1994; 54:22:5953–5958
     [Google Scholar]
  16. Brudvik KW, Taskén K. Modulation of T cell immune functions by the prostaglandin E(2)–cAMP pathway in chronic inflammatory states. Br J Pharmacol. 2012; 166:2:411–419
     [Google Scholar]
  17. Schlemper RJ, Riddell RH, Kato Y, Borchard F, Cooper HS, Dawsey SM, Dixon MF, Fenoglio-Preiser CM, Fléjou J-F, Geboes K, Hattori T, Hirota T, Itabashi M, Iwafuchi M, Iwashita A, Kim YI, Kirchner T, Klimpfinger M, Koike M, Lauwers GY, Lewin KJ, Oberhuber G, Offner F, Price AB, Rubio CA, Shimizu M, Shimoda T, Sipponen P, Solcia E, Stolte M, Watanabe H, Yamabe H. The Vienna classification of gastrointestinal epithelial neoplasia. Gut. 2000; 47:2:251–255
     [Google Scholar]
  18. Beahrs OH. Colorectal cancer staging as a prognostic feature. Cancer. 1982; 50:11:2615–2617
     [Google Scholar]
  19. Rask K, Zhu Y, Wang W, Hedin L, Sundfeldt K. Ovarian epithelial cancer: a role for PGE2-synthesis and signalling in malignant transformation and progression. Mol Cancer. 2006; 5::62
     [Google Scholar]
  20. Backlund MG, Mann JR, Dubois RN. Mechanisms for the prevention of gastrointestinal cancer: the role of prostaglandin E 2. Oncology. 2005; 69:Suppl. 1:28–32
     [Google Scholar]
  21. Houchen CW, Sturmoski MA, Anant S, Breyer RM, Stenson WF. Prosurvival and antiapoptotic effects of PGE2 in radiation injury are mediated by EP2 receptor in intestine. Am J Physiol Gastrointest Liver Physiol. 2003; 284:3:G490–G498
     [Google Scholar]
  22. Müller-Decker K, Albert C, Lukanov T, Winde G, Marks F, Fürstenberger G. Cellular localization of cyclo-oxygenase isozymes in Crohn's disease and colorectal cancer. Int J Colorectal Dis. 1999; 14:4–5:212–218
     [Google Scholar]
  23. Hull MA, Ko SC, Hawcroft G. Prostaglandin EP receptors: targets for treatment and prevention of colorectal cancer? Mol Cancer Ther. 2004; 3:8:1031–1039
     [Google Scholar]
  24. Sonoshita M, Takaku K, Sasaki N, Sugimoto Y, Ushikubi F, Narumiya S, Oshima M, Taketo MM. Acceleration of intestinal polyposis through prostaglandin receptor EP2 in Apc(Delta 716) knockout mice. Nat Med. 2001; 7:9:1048–1051
     [Google Scholar]
  25. Takeda H, Sonoshita M, Oshima H, Sugihara K, Chulada PC, Langenbach R, Oshima M, Taketo MM. Cooperation of cyclooxygenase 1 and cyclooxygenase 2 in intestinal polyposis. Cancer Res. 2003; 63:16:4872–4877
     [Google Scholar]
  26. Mauritz I, Westermayer S, Marian B, Erlach N, Grusch M, Holzmann K. Prostaglandin E(2) stimulates progression-related gene expression in early colorectal adenoma cells. Br J Cancer. 2006; 94:11:1718–1725
     [Google Scholar]
  27. Hao X, Bishop AE, Wallace M, Wang H, Willcocks TC, Maclouf J, Polak JM, Knight S, Talbot IC. Early expression of cyclo-oxygenase-2 during sporadic colorectal carcinogenesis. J Pathol. 1999; 187:3:295–301
     [Google Scholar]
  28. Hull MA, Booth JK, Tisbury A, Scott N, Bonifer C, Markham AF, Coletta PL. Cyclooxygenase 2 is up-regulated and localized to macrophages in the intestine of min mice. Br J Cancer. 1999; 79:9-10:1399–1405
     [Google Scholar]
  29. Chapple KS, Cartwright EJ, Hawcroft G, Tisbury A, Bonifer C, Scott N, Windsor AC, Guillou PJ, Markham AF, Coletta PL, Hull MA. Localization of cyclooxygenase-2 in human sporadic colorectal adenomas. Am J Pathol. 2000; 156:2:545–553
     [Google Scholar]
  30. Sonoshita M, Takaku K, Oshima M, Sugihara K, Taketo MM. Cyclooxygenase-2 expression in fibroblasts and endothelial cells of intestinal polyps. Cancer Res. 2002; 62:23:6846–6849
     [Google Scholar]
  31. Hardwick JC, van den Brink GR, Offerhaus GJ, van Deventer SJ, Peppelenbosch MP. NF-kappaB, p38 MAPK and JNK are highly expressed and active in the stroma of human colonic adenomatous polyps. Oncogene. 2001; 20:7:819–827
     [Google Scholar]
  32. Tatsu K, Hayashi S, Shimada I, Matsui K. Cyclooxygenase-2 in sporadic colorectal polyps: immunohistochemical study and its importance in the early stages of colorectal tumorigenesis. Pathol Res Pract. 2005; 201:6:427–433
     [Google Scholar]
  33. Sheehan KM, O'Connell F, O'Grady A, Conroy RM, Leader MB, Byrne MF, Murray FE, Kay EW. The relationship between cyclooxygenase-2 expression and characteristics of malignant transformation in human colorectal adenomas. Eur J Gastroenterol Hepatol. 2004; 16:6:619–625
     [Google Scholar]
  34. Elder DJ, Baker JA, Banu NA, Moorghen M, Paraskeva C. Human colorectal adenomas demonstrate a size-dependent increase in epithelial cyclooxygenase-2 expression. J Pathol. 2002; 198:4:428–434
     [Google Scholar]
  35. Ko SC, Chapple KS, Hawcroft G, Coletta PL, Markham AF, Hull MA. Paracrine cyclooxygenase-2-mediated signalling by macrophages promotes tumorigenic progression of intestinal epithelial cells. Oncogene. 2002; 21:47:7175–7186
     [Google Scholar]
  36. Baratelli F, Lin Y, Zhu L, Yang SC, Heuzé-Vourc'h N, Zeng G, Reckamp K, Dohadwala M, Sharma S, Dubinett SM. Prostaglandin E2 induces FOXP3 gene expression and T regulatory cell function in human CD4+T cells. J Immunol. 2005; 175:3:1483–1490
     [Google Scholar]
  37. Sharma S, Yang S-C, Zhu L, Reckamp K, Gardner B, Baratelli F, Huang M, Batra RK, Dubinett SM. Tumor cyclooxygenase-2/prostaglandin E2-dependent promotion of FOXP3 expression and CD4+ CD25+T regulatory cell activities in lung cancer. Cancer Res. 2005; 65:12:5211–5220
     [Google Scholar]
  38. Liu VC, Wong LY, Jang T, Shah AH, Park I, Yang X, Zhang Q, Lonning S, Teicher BA, Lee C. Tumor evasion of the immune system by converting CD4+CD25- T cells into CD4+CD25+T regulatory cells: role of tumor-derived TGF-beta. J Immunol. 2007; 178:5:2883–2892
     [Google Scholar]
  39. de Souza AP, Bonorino C. Tumor immunosuppressive environment: effects on tumor-specific and nontumor antigen immune responses. Expert Rev Anticancer Ther. 2009; 9:9:1317–1332
     [Google Scholar]
  40. Canna K, McMillan DC, McKee RF, McNicol AM, Horgan PG, McArdle CS. Evaluation of a cumulative prognostic score based on the systemic inflammatory response in patients undergoing potentially curative surgery for colorectal cancer. Br J Cancer. 2004; 90:9:1707–1709
     [Google Scholar]
  41. Dimberg J, Samuelsson A, Hugander A, Soderkvist P. Differential expression of cyclooxygenase 2 in human colorectal cancer. Gut. 1999; 45:5:730–732
     [Google Scholar]
  42. Kamei D, Murakami M, Nakatani Y, Ishikawa Y, Ishii T, Kudo I. Potential role of microsomal prostaglandin E synthase-1 in tumorigenesis. J Biol Chem. 2003; 278:21:19396–19405
     [Google Scholar]
  43. Mutoh M, Watanabe K, Kitamura T, Shoji Y, Takahashi M, Kawamori T, Tani K, Kobayashi M, Maruyama T, Kobayashi K, Ohuchida S, Sugimoto Y, Narumiya S, Sugimura T, Wakabayashi K. Involvement of prostaglandin E receptor subtype EP4 in colon carcinogenesis. Cancer Res. 2002; 62:1:28–32
     [Google Scholar]
  44. Seno H, Oshima M, Ishikawa TO, Oshima H, Takaku K, Chiba T, Narumiya S, Taketo MM. Cyclooxygenase 2- and prostaglandin E(2) receptor EP(2)-dependent angiogenesis in Apc(Delta716) mouse intestinal polyps. Cancer Res. 2002; 62:2:506–511
     [Google Scholar]
/content/journals/10.5339/avi.2013.5
Loading
Role of prostaglandins in colorectal tumorigenesis: Localization and expression of COX-1, COX-2, microsomal Prostaglandin E Synthase-1 and the EP2 receptor
Avicenna 2013, 5 (2013); https://doi.org/10.5339/avi.2013.5
/content/journals/10.5339/avi.2013.5
/content/journals/10.5339/avi.2013.5
Loading

Data & Media loading...

  • Article Type: Research Article

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error