title: Housing temperature-induced stress drives therapeutic resistance in murine tumour models through β2-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 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.
authors.affiliation: Department of Immunology, Roswell Park Cancer Institute, Center for Genetics and Pharmacology, Elm and Carlton Streets, Buffalo, New York 14263, USA.
authors.forename: Jason W-L
authors.initials: JW
authors.lastname: Eng
authors.affiliation: Department of Immunology, Roswell Park Cancer Institute, Center for Genetics and Pharmacology, Elm and Carlton Streets, Buffalo, New York 14263, USA.
authors.forename: Chelsey B
authors.initials: CB
authors.lastname: Reed
authors.affiliation: Department of Immunology, Roswell Park Cancer Institute, Center for Genetics and Pharmacology, Elm and Carlton Streets, Buffalo, New York 14263, USA.
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Kokolus
authors.affiliation: Department of Immunology, Roswell Park Cancer Institute, Center for Genetics and Pharmacology, Elm and Carlton Streets, Buffalo, New York 14263, USA.
authors.forename: Rosemarie
authors.initials: R
authors.lastname: Pitoniak
authors.affiliation: Department of Immunology, Roswell Park Cancer Institute, Center for Genetics and Pharmacology, Elm and Carlton Streets, Buffalo, New York 14263, USA.
authors.forename: Adam
authors.initials: A
authors.lastname: Utley
authors.affiliation: Department of Immunology, Roswell Park Cancer Institute, Center for Genetics and Pharmacology, Elm and Carlton Streets, Buffalo, New York 14263, USA.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Bucsek
authors.affiliation: Department of Medicine, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, New York 14263, USA.
authors.forename: Wen Wee
authors.initials: WW
authors.lastname: Ma
authors.affiliation: Department of Immunology, Roswell Park Cancer Institute, Center for Genetics and Pharmacology, Elm and Carlton Streets, Buffalo, New York 14263, USA.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Repasky
authors.affiliation: Department of Immunology, Roswell Park Cancer Institute, Center for Genetics and Pharmacology, Elm and Carlton Streets, Buffalo, New York 14263, USA.
authors.forename: Bonnie L
authors.initials: BL
authors.lastname: Hylander
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000418:Albumins / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D017239:Paclitaxel / Q000494:pharmacology; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D013312:Stress, Physiological; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000494:pharmacology; D013696:Temperature; D023041:Xenograft Model Antitumor Assays; D051020:bcl-X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: C520255:130-nm albumin-bound paclitaxel; D000318:Adrenergic beta-Agonists; D000418:Albumins; D000970:Antineoplastic Agents; C494812:Bcl2l1 protein, mouse; D019253:Proto-Oncogene Proteins c-bcl-2; D018343:Receptors, Adrenergic, beta-2; D053221:TNF-Related Apoptosis-Inducing Ligand; D051020:bcl-X Protein; C052617:Bcl2 protein, mouse; D007545:Isoproterenol; D017239:Paclitaxel; D002945:Cisplatin