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

JWL Eng, CB Reed, KM Kokolus, R Pitoniak… - Nature …, 2015 - nature.com
JWL Eng, CB Reed, KM Kokolus, R Pitoniak, A Utley, MJ Bucsek, WW Ma, EA Repasky…
Nature communications, 2015nature.com
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 …
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.
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