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

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  • Jason W.-L. Eng

    (Roswell Park Cancer Institute, Center for Genetics and Pharmacology)

  • Chelsey B. Reed

    (Roswell Park Cancer Institute, Center for Genetics and Pharmacology)

  • Kathleen M. Kokolus

    (Roswell Park Cancer Institute, Center for Genetics and Pharmacology)

  • Rosemarie Pitoniak

    (Roswell Park Cancer Institute, Center for Genetics and Pharmacology)

  • Adam Utley

    (Roswell Park Cancer Institute, Center for Genetics and Pharmacology)

  • Mark J. Bucsek

    (Roswell Park Cancer Institute, Center for Genetics and Pharmacology)

  • Wen Wee Ma

    (Roswell Park Cancer Institute)

  • Elizabeth A. Repasky

    (Roswell Park Cancer Institute, Center for Genetics and Pharmacology)

  • Bonnie L. Hylander

    (Roswell Park Cancer Institute, Center for Genetics and Pharmacology)

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.

Suggested Citation

  • 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, 2015. "Housing temperature-induced stress drives therapeutic resistance in murine tumour models through β2-adrenergic receptor activation," Nature Communications, Nature, vol. 6(1), pages 1-13, May.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7426
    DOI: 10.1038/ncomms7426
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