Aggressive fibromatosis is a benign fibroproliferative tumour that can occur as a sporadic lesion or a manifestation in patients with familial syndromes, such as familial adenomatous polyposis. Tumours are characterized by the stabilization of β-catenin and the activation of β-catenin-mediated transcription. Current treatment results are far from ideal, and recurrence rates are high. As a result, there remains a need for more effective therapeutic strategies. In this work, we demonstrate the effect of hedgehog signalling inhibition on aggressive fibromatosis tumour development and β-catenin modulation. We found that hedgehog inhibition decreased cell viability and proliferation as well as total β-catenin levels in human aggressive fibromatosis tumour cells in vitro. Furthermore, following hedgehog inhibition in Apc+/Apc1638N aggressive fibromatosis mouse model, the number and volume of the tumours formed was reduced. Together, this work suggests that hedgehog signalling inhibitor agents are potential candidates to effectively manage aggressive fibromatosis.
| Identifer | oai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/33213 |
| Date | 20 November 2012 |
| Creators | Ghanbari Azarnier, Ronak |
| Contributors | Alman, Benjamin |
| Source Sets | University of Toronto |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
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