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Cyclooxygenase-two (COX-2) modulates proliferation in aggressive fibromatosis (desmoid tumor)

Oncogene volume 20, pages 451–460 (2001)Cite this article

Abstract

Aggressive fibromatosis is a locally invasive soft tissue lesion. Seventy-five per cent of cases harbor a somatic mutation in either the APC or β-catenin genes, resulting in β-catenin protein stabilization. Cyclooxygenase-2 (COX-2) is an enzyme involved in prostaglandin synthesis that modulates the formation of colonic neoplasia, especially in cases due to mutations resulting in β-catenin stabilization. Human aggressive fibromatoses and lesions from the Apc+/Apc1638N mouse (a murine model for Apc-driven fibromatosis) demonstrated elevated COX-2 levels. COX-2 blockade either by the selective agent DFU or by non-selective COX blocking agents results in reduced proliferation in human tumor cell cultures. Breeding mice with Cox-2−/− mice resulted in no difference in number of aggressive fibromatoses formed, but in a smaller tumor size, while there was a decrease in number of GI lesions by 50%. Mice fed various COX blocking agents also showed a decline in tumor size. COX-2 expression was regulated by tcf-dependent transcription in this lesion. COX-2 partially regulates proliferation due to β-catenin stabilization in aggressive fibromatosis. Although COX blockade alone does not cause tumor regression, this data suggests that it may have a role as an adjuvant therapy to slow tumor growth in this lesion.

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References

  • Abramson SB and Weissmann G. . 1989 Arthritis Rheum. 32: 1–9.

  • Ahnen DJ. . 1998 Eur. J. Surg. (Suppl.) 582: 111–114.

  • Alman BA, Pajerski ME, Diaz-Cano S, Corboy K and Wolfe HJ. . 1997a Diagn. Mol. Pathol. 6: 98–101.

  • Alman BA, Li C, Pajerski ME, Diaz-Cano S and Wolfe HJ. . 1997b Am. J. Pathol. 151: 329–334.

  • Alman BA, Greel DA, Ruby LK, Goldberg MJ and Wolfe HJ. . 1996 J. Orthop. Res. 14: 722–728.

  • Alman BA, Goldberg MJ, Naber SP, Galanopoulos T, Antoniades HN and Wolfe HJ. . 1992 J. Pediatr. Orthop. 12: 1–10.

  • Alman BA, Naber SP, Terek RM, Jiranek WA, Goldberg MJ and Wolfe HJ. . 1995 J. Orthop. Res. 13: 67–77.

  • Beliveau P and Graham AM. . 1984 Colon Rectum 27: 53–54.

  • Black SC, Brideau C, Cirino M, Belley M, Bosquet J, Chan CC and Rodger IW. . 1998 J. Cardiovas. Pharmacol. 32: 686–694.

  • Castano E, Bartrons R and Gil J. . 2000 J. Pharm. Exp. Ther. 293: 509–513.

  • Chan CC, Panneton M, Taylor AM, Therien M and Rodger IW. . 1997 Eur. J. Pharmacol. 327: 221–225.

  • DuBois RN, Shao J, Tsujii M, Sheng H and Beauchamp RD. . 1996 Cancer Res. 56: 733.

  • Dinchuk JE, Car BD, Focht RJ, Johnston JJ, Jaffee BD, Covington MB, Contel NR, Eng VM, Collins RJ, Czerniak PM, et al. 1995 Nature 378: 406–409.

  • Eccles DM, van der Luijt R, Breukel C, Bullman H, Bunyan D, Fisher A, Barber J, du Boulay C, Primrose J, Burn J and Fodde R. . 1996 Am. J. Hum. Genet. 59: 1193–1201.

  • Erickson BA, Longo WE, Panesar N, Mazuski JE and Kaminski DL. . 1999 J. Surg. Res. 81: 101–107.

  • Fodde R, Edelmann W, Yang K, van Leeuwen C, Carlson C, Renault B, Bruekel C, Alt E, Lipkin M, Khan PM, et al. 1994 Proc. Natl. Acad. Sci. USA 91: 8986–8973.

  • Giardella FM, Petersen GM, Piantadosi S, Gruber SB, Traboulsi EI, Offerhaus GJ, Muro K, Krush AJ, Booker SV, Luce MC, et al. 1997 Gut 40: 521–525.

  • Groden J, Thliveris A, Samowitz W, Carlson M, Gelbert L, Albertsen H, Joslyn G, Steven J, Spiro L, Robertson M, et al. 1991 Cell 66: 589–600.

  • Gustafson-Svad C, Lilja I, Hallbook O and Sjodahl R. . 1996 Gut 38: 79–84.

  • Hanif R, Pittas A, Feng Y, Koutsos MI, Qiao L, Staiano-Coico L, Shiff SI and Rigas B. . 1996 Biochem. Pharmacol. 52: 237–245.

  • He T-C, Chan TA, Vogelstein B and Kinzler KW. . 1999 Cell 99: 335–345.

  • Hial V, DeMello MC, Horakova Z and Beaven MA. . 1977 J. Pharmacol. Exp. Ther. 202: 446–454.

  • Hsi LC, Angerman-Stewart J and Eling TE. . 1999 Carcinogenesis 20: 2045–2049.

  • Kinzler KW, Nilbert MC, Su LK, Vogelstein B, Bryan TM, Levy DB, Smith KJ, Presinger AC, Hedge P, McKechnie D, et al. 1991 Science 253: 661–665.

  • Kirsch WM. . 1991 Am. J. Surg. 161: 416–421.

  • Lackner H, Urban C, Kerbl R, Schwinger W and Beham A. . 1997 Cancer 80: 334–340.

  • Lattes R. (ed.). . 1980 Tumors of the Soft Tissues. Armed Forces Institute of Pathology: Washington DC. pp.1–30.

  • Li C, Bapat B and Alman BA. . 1998 Am. J. Pathol. 153: 709–714.

  • Mei JM, Hord NG, Winterstein DF, Donald SP and Phang JM. . 1999 Carcinogenesis 20: 737–740.

  • Miller JR, Hocking AM, Brown JD and Moon RT. . 1999 Oncogene 18: 7860–7872.

  • Morin PJ, Sparks AB, Korinek V, Barker N, Clevers H, Vogelstein B and Kinzler KW. . 1997 Science 275: 1787–1790.

  • Nguyen KD and Lee DA. . 1993 Ext. Eye Res. 57: 97–105.

  • Oshima M, Dinchuk JE, Kargman SL, Oshima H, Hancock B, Kwong E, Trzaskos JM, Evans JF and Taketo MM. . 1996 Cell 87: 803–809.

  • Posner MC, Shiu MH, Newsome JL, Hajdu SI, Gaynor JJ and Brennan MF. . 1989 Arch. Surg. 124: 191–196.

  • Roose J and Clevers H. . 1999 Biochim. Biophys. Acta. 1424: M23–M37.

  • Schmidt A, Endo N, Rutledge SJ, Vogel R, Shinar D and Rodan GA. . 1992 Mol. Endocrinol. 6: 1634–1641.

  • Scott RJ, Froggart NJ, Trembath RC, Evans DGR, Hodgson SV and Maher ER. . 1996 Hum. Mol. Genet. 5: 1921–1924.

  • Sheng H, Shao J, Kirkland SC, Isakson P, Coffey RJ, Morrow J, Beauchamp RD and DuBois RN. . 1997 J. Clin. Invest. 99: 2254–2259.

  • Smits R, van der Houven van Oordt W, Luz A, Zurcher C, Jagmohan-Changur S, Bruekel C, Khan PM and Fodde R. . 1998 Gastroenterology 114: 275–283.

  • Sparks AB, Morin PJ, Vogelstein B and Kinzler KW. . 1998 Cancer Res. 58: 1130–1134.

  • Tejpar S, Nollet F, Li C, Wunder JS, Michils G, dal Cin P, Van Cutsem E, Bapat B, van Roy F, Cassiman JJ and Alman BA. . 1999 Oncogene 18: 6615–6620.

  • Tetsu O and McCormick F. . 1999 Nature 398: 422–426.

  • Tsujii M and DuBois RN. . 1995 Cell 83: 493–501.

  • Tsujii M, Kawano S, Tsuji S, Sawaoka H, Hori M and DuBois RN. . 1998 Cell 93: 705–716.

  • van der Houven van Oordt CW, Smits R, Schouten TG, Houwing-Duistermaat JJ, Williamson SL, Luz A, Meera Khan P, Van der Eb AJ, Breuer ML and Fodde R. . 1999 Genes Chrom. Cancer 24: 191–198.

  • Waddell WR, Gerner RE and Reich MP. . 1983 J. Surg. Oncol. 22: 197–211.

  • Watson AJ. . 1998 Histo. Histopath. 13: 591–597.

  • Williams CS, Mann M and DuBois RN. . 1999 Oncogene 18: 7908–7916.

  • Williams CS, Smalley W and DuBois RN. . 1997 J. Clin. Invest. 100: 1325–1329.

  • Wolf LA and Laster SM. . 1999 Cell Biochem. Biophys. 30: 353–681.

  • Zhang X, Morham SG, Langenbach R and Young DA. . 1999 J. Exp. Med. 190: 451–460.

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Acknowledgements

Funded by grants from the National Cancer institute of Canada with funds from the Terry Fox Run, grant number 9129, to BA Alman; The Medical Research Council of Canada, grant number MT-15136, to BA Alman; and The Dutch Cancer Society (KWF), grant number RUL-98-1652, to R Smits and R Fodde. The DFU, MF Tricyclic and Sulindac formulated into mouse chow, the control mouse diet, and the DFU for use in cell cultures were all obtained from Merck Frosst, Quebec, Canada. The drug levels in the mice were tested at Merck Frosst, Quebec, Canada. The ΔN-tcf-4E was obtained from Osamu Tetsu and Frank McCormick, who produced this from a construct they obtained from Hans Clevers.

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  1. Program in Developmental Biology and Department of Surgery, The Hospital for Sick Children and the University of Toronto, Toronto, Ontario, Canada

    Raymond Poon, Catherine Li, Michael Kong, Sophia Cheon, Chunying Yu & Benjamin A Alman

  2. Department of Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands

    Ron Smits, Shantie Jagmohan-Changur & Riccardo Fodde

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  1. Raymond Poon
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Poon, R., Smits, R., Li, C. et al. Cyclooxygenase-two (COX-2) modulates proliferation in aggressive fibromatosis (desmoid tumor). Oncogene 20, 451–460 (2001). https://doi.org/10.1038/sj.onc.1204107

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