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

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57 Scopus citations

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 2-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.

Original languageEnglish (US)
Article number6426
JournalNature communications
Volume6
DOIs
StatePublished - Mar 10 2015

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Eng, J. W. L., Reed, C. B., Kokolus, K. M., Pitoniak, R., Utley, A., Bucsek, M. J., Ma, W. W., Repasky, E. A., & Hylander, B. L. (2015). Housing temperature-induced stress drives therapeutic resistance in murine tumour models through β2-adrenergic receptor activation. Nature communications, 6, [6426]. https://doi.org/10.1038/ncomms7426