Return to search

Hedgehog Signalling and Tumour-initiating cells as Radioresistance Factors in Esophageal Adenocarcinoma

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.

Identiferoai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/33560
Date27 November 2012
CreatorsTeichman, Jennifer
ContributorsLiu, Geoffrey, Ailles, Laurie
Source SetsUniversity of Toronto
Languageen_ca
Detected LanguageEnglish
TypeThesis

Page generated in 0.002 seconds