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Housing temperature-induced stress drives therapeutic resistance in murine tumour models through ?2-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 ?-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.

SUBMITTER: Eng JW

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

REPOSITORIES: biostudies-literature

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

Eng Jason W-L JW Reed Chelsey B CB Kokolus Kathleen M KM Pitoniak Rosemarie R Utley Adam A Bucsek Mark J MJ Ma Wen Wee WW Repasky Elizabeth A EA Hylander Bonnie L BL

Nature communications 20150310

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 ...[more]

PMID: 25756236

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Dataset Information

Housing temperature-induced stress drives therapeutic resistance in murine tumour models through ?2-adrenergic receptor activation.

Publications

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

Similar Datasets

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