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

Oncogene. 2001 Jan 25;20(4):451-60. doi: 10.1038/sj.onc.1204107.


Aggressive fibromatosis is a locally invasive soft tissue lesion. Seventy-five per cent of cases harbor a somatic mutation in either the APC or beta-catenin genes, resulting in beta-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 beta-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 beta-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cyclooxygenase 2
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors / pharmacology
  • Cytoskeletal Proteins / isolation & purification
  • Fibromatosis, Aggressive / etiology*
  • Fibromatosis, Aggressive / pathology
  • Humans
  • Isoenzymes / antagonists & inhibitors
  • Isoenzymes / genetics
  • Isoenzymes / metabolism*
  • Male
  • Membrane Proteins
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Prostaglandin-Endoperoxide Synthases / genetics
  • Prostaglandin-Endoperoxide Synthases / metabolism*
  • Receptors, Cytoplasmic and Nuclear / isolation & purification
  • Trans-Activators*
  • Transcription Factors / isolation & purification
  • beta Catenin


  • CTNNB1 protein, human
  • CTNNB1 protein, mouse
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors
  • Cytoskeletal Proteins
  • Isoenzymes
  • Membrane Proteins
  • Receptors, Cytoplasmic and Nuclear
  • Trans-Activators
  • Transcription Factors
  • beta Catenin
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases