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Updated: Jul 12, 2026

A Mouse Model to Investigate the Role of Cancer-Associated Fibroblasts in Tumor Growth
06:35

A Mouse Model to Investigate the Role of Cancer-Associated Fibroblasts in Tumor Growth

Published on: December 22, 2020

Cyclooxygenase-2 and platelet-derived growth factor receptors as potential targets in treating aggressive

Stefano Signoroni1, Milo Frattini, Tiziana Negri

  • 1Experimental Molecular Pathology, Department of Pathology, Fondazione IRCSS Istituto Nazionale dei Tumori, Milan, Italy.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|September 6, 2007
PubMed
Abstract

Insights

Aggressive fibromatosis involves WNT pathway alterations activating COX-2 and PDGF receptors. Combined NSAID and tyrosine kinase inhibitor therapy may benefit patients with desmoid tumors.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Aggressive fibromatosis (desmoid tumors) are locally invasive neoplasms.
  • Understanding the molecular drivers is crucial for identifying new therapeutic targets.

Purpose of the Study:

  • To investigate the molecular mechanisms underlying aggressive fibromatosis.
  • To identify potential new pharmacologic targets for desmoid tumors.

Main Methods:

  • Tumor specimens from 14 patients were analyzed.
  • Methods included immunohistochemistry, biochemistry, molecular, and cytogenetic analyses.
  • Key genes and proteins investigated: APC, CTNNB1 (beta-catenin), COX-2, PDGFRA, PDGFRB, PDGFA, PDGFB, and KIT.

Main Results:

  • Activating CTNNB1 (beta-catenin) mutations were found in sporadic cases, correlating with WNT pathway alterations.
  • COX-2 overexpression and PDGFRA/PDGFRB activation were observed in all cases.
  • PDGFRA/PDGFRB activation was sustained by an autocrine/paracrine loop.

Conclusions:

  • Aggressive fibromatosis exhibits WNT/oncogene pathway alterations.
  • COX-2 mediated coactivation of PDGFRA and PDGFRB is a key feature.
  • Combined treatment with NSAIDs and tyrosine kinase inhibitors may be beneficial.

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