Housing temperature-induced stress drives therapeutic resistance in murine tumour models through β2-adrenergic receptor activation.

ABSTRACT: Cancer research relies heavily on murine models for evaluating the anti-tumour efficacy of therapies. Here we show that the sensitivity of several pancreatic tumour models to cytotoxic therapies is significantly increased when mice are housed at a thermoneutral ambient temperature of 30 °C compared with the standard temperature of 22 °C. Further, we find that baseline levels of norepinephrine as well as the levels of several anti-apoptotic molecules are elevated in tumours from mice housed at 22 °C. The sensitivity of tumours to cytotoxic therapies is also enhanced by administering a β-adrenergic receptor antagonist to mice housed at 22 °C. These data demonstrate that standard housing causes a degree of cold stress sufficient to impact the signalling pathways related to tumour-cell surviva

SUBMITTER: Eng JW 

PROVIDER: S-EPMC4471870 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature