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

Jason W-L Eng, Chelsey B Reed, Kathleen M Kokolus, Rosemarie Pitoniak, Adam Utley, Mark J Bucsek, Wen Wee Ma, Elizabeth A Repasky, Bonnie L Hylander

Index: Nat. Commun. 6 , 6426, (2015)

Full Text: HTML

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 survival and affect the outcome of pre-clinical experiments. Furthermore, these data highlight the significant role of host physiological factors in regulating the sensitivity of tumours to therapy.