The effect of housing temperature on the growth of CT26 tumor expressing fluorescent protein EGFP

To date, the effect of housing temperature on tumor development in the immunocompetent mice has been studied on poorly immunogenic cancer models. Standard housing temperature 20–26°C was shown to cause chronic metabolic cold stress and promote tumor progression via suppression of the antitumor immune response, whereas a thermoneutral temperature 30-31°C was more preferable for normal metabolism of mice and inhibited tumor growth. Our work represents the first attempt to discover the potential effect of housing temperature on the development of highly immunogenic tumor. EGFP-expressing murine colon carcinoma CT26 generated in Balb/c mice was used as a tumor model. No statistically significant differences were shown in tumor incidences and growth rates at 20°С, 25°С and 30°С for non-modified CT26. Maintaining mice challenged with CT26-EGFP cells at 30°С led to complete inhibition of tumor development. In summary, we demonstrated that the housing temperature is important for the regulation of growth of highly immunogenic tumors in mice through antitumor immunity.

[1]  V. Cicinnati,et al.  Immunogenicity of enhanced green fluorescent protein (EGFP) in BALB/c mice: identification of an H2-Kd-restricted CTL epitope , 2000, Gene Therapy.

[2]  Michael R Hamblin,et al.  A green fluorescent protein-expressing murine tumour but not its wild-type counterpart is cured by photodynamic therapy , 2006, British Journal of Cancer.

[3]  C. Schmitt,et al.  Stromal Interferon-γ Signaling and Cross-Presentation Are Required to Eliminate Antigen-Loss Variants of B Cell Lymphomas in Mice , 2012, PloS one.

[4]  C. Karp.  Unstressing intemperate models: how cold stress undermines mouse modeling , 2012, The Journal of experimental medicine.

[5]  Diana V Yuzhakova,et al.  CT26 murine colon carcinoma expressing the red fluorescent protein KillerRed as a highly immunogenic tumor model , 2015, Journal of biomedical optics.

[6]  J. Lustgarten,et al.  Aged Mice Develop Protective Antitumor Immune Responses with Appropriate Costimulation1 , 2004, The Journal of Immunology.

[7]  Udo Albus,et al.  Book Review: Guide for the Care and use of Laboratory Animals , 1998 .

[8]  B. Vogelstein,et al.  Induction in a murine tumor of immunogenic tumor variants by transfection with a foreign gene. , 1988, Cancer research.

[9]  D. Skelton,et al.  The enhanced green fluorescent protein (eGFP) is minimally immunogenic in C57BL/6 mice , 2001, Gene Therapy.

[10]  B. Povinelli,et al.  Stressful Presentations: Mild Cold Stress in Laboratory Mice Influences Phenotype of Dendritic Cells in Naïve and Tumor-Bearing Mice , 2013, Front. Immunol..

[11]  Jeremy Terrien,et al.  Behavioral thermoregulation in mammals: a review. , 2011, Frontiers in bioscience.

[12]  B. Hylander,et al.  Housing temperature-induced stress drives therapeutic resistance in murine tumour models through β2-adrenergic receptor activation , 2015, Nature Communications.

[13]  C. Sautès-Fridman,et al.  Immune adaptive microenvironment profiles in intracerebral and intrasplenic lymphomas share common characteristics , 2011, Clinical and experimental immunology.

[14]  C. J. Gordon,et al.  Baseline tumor growth and immune control in laboratory mice are significantly influenced by subthermoneutral housing temperature , 2013, Proceedings of the National Academy of Sciences.

[15]  D. Kohn,et al.  Immune response to green fluorescent protein: implications for gene therapy , 1999, Gene Therapy.

[16]  W. Falk,et al.  GFP-transfected tumor cells are useful in examining early metastasis in vivo, but immune reaction precludes long-term tumor development studies in immunocompetent mice , 2004, Clinical & Experimental Metastasis.