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

Research output: Contribution to journalArticlepeer-review

74 Scopus citations


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
StatePublished - Mar 10 2015

ASJC Scopus subject areas

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


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