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

• DOI: 10.1038/ncomms7426
• Publication Date: 2015-03-10T15:53:59Z
• Authors: 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
• Keywords: 0301 basic medicine; Paclitaxel; Isoproterenol; Antineoplastic Agents; Apoptosis; Mice, SCID; Adrenergic beta-Agonists; 3. Good health; Gene Expression Regulation, Neoplastic; Mice, Inbred C57BL; Pancreatic Neoplasms; Mice; 03 medical and health sciences; Proto-Oncogene Proteins c-bcl-2; Drug Resistance, Neoplasm; Stress, Physiological; Albumins; Cell Line, Tumor; Animals; Humans; Receptors, Adrenergic, beta-2; Cisplatin; Signal Transduction

Cancer research relies heavily on murine models for evaluating the anti-tumour efficacy of therapies. Here we show that sensitivity several pancreatic tumour to cytotoxic therapies is significantly increased when mice are housed at a thermoneutral ambient temperature 30 °C compared with standard 22 °C. Further, find baseline levels norepinephrine as well anti-apoptotic molecules elevated in tumours from The also enhanced by administering β-adrenergic receptor antagonist These data demonstrate housing causes degree cold stress sufficient impact signalling pathways related tumour-cell survival and affect outcome pre-clinical experiments. Furthermore, these highlight significant role host physiological factors regulating therapy. Anticancer treatments tested below thermoneutrality which represents chronic cold-stress. Eng et al. have activated responses leading therapeutic resistance inhibiting adrenergic signaling increases anticancer