Clinical management of esophageal adenocarcinoma (EAC) relies on radiation therapy, yet radioresistance is a pervasive challenge in this disease. The mechanisms of EAC radioresistance remain largely unknown due to a paucity of validated preclinical models. The present studies report on the development of seven primary xenograft models established from patient tumours. These models are used to interrogate the range of radiosensitivities and mechanisms of radioresistance in EAC tumours. We found that radiation enriches the tumour-initiating cell population in two xenograft lines tested. Furthermore, three tested xenograft lines respond to irradiation by upregulating Hedgehog transcripts, a pathway involved in stem cell maintenance and proliferation. Upregulation occurs in autocrine and paracrine patterns simultaneously, suggesting that Hedgehog signalling may have a complex role in the radioresponse of EAC tumours. These findings suggest that inhibiting stem cell pathways in combination with radiotherapy may have an important role in the clinical management of EAC.
| Identifer | oai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/33560 |
| Date | 27 November 2012 |
| Creators | Teichman, Jennifer |
| Contributors | Liu, Geoffrey, Ailles, Laurie |
| Source Sets | University of Toronto |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
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