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Behav Brain Res. 2017 Jul 14;330:108-117. doi: 10.1016/j.bbr.2017.05.011. Epub 2017 May 4.

Novel rodent model of breast cancer survival with persistent anxiety-like behavior and inflammation.

Author information

1
Institute for Behavioral Medicine Research, Ohio State University Wexner Medical Center, Columbus, OH, USA; Department of Psychiatry and Behavioral Health, Ohio State University, Columbus, OH, USA; Department of Neuroscience, Ohio State University, Columbus, OH, USA; Behavioral Neuroendocrinology Group, Ohio State University, Columbus, OH, USA; Arthur G. James Comprehensive Cancer Center and Solove Research Institute, Ohio State University, Columbus, OH USA. Electronic address: leah.pyter@osumc.edu.
2
Arthur G. James Comprehensive Cancer Center and Solove Research Institute, Ohio State University, Columbus, OH USA.
3
Arthur G. James Comprehensive Cancer Center and Solove Research Institute, Ohio State University, Columbus, OH USA; Department of Surgery, Ohio State University, Columbus, OH, USA.
4
Institute for Behavioral Medicine Research, Ohio State University Wexner Medical Center, Columbus, OH, USA.
5
Institute for Behavioral Medicine Research, Ohio State University Wexner Medical Center, Columbus, OH, USA; Department of Psychiatry and Behavioral Health, Ohio State University, Columbus, OH, USA.

Abstract

Breast cancer survivors are an expanding population that is troubled by lasting mental health problems, including depression and anxiety. These issues reduce quality-of-life throughout survivorhood. Research indicates that tumor biology, cancer treatments, and stress contribute to these mood disturbances. Although the mechanisms underlying these various causes remain under investigation, neuroinflammation is a leading hypothesis. To date, rodent models of recurrence-free tumor survival for understanding mechanisms by which these behavioral issues persist after cancer are lacking. Here, we test the extent to which potential behavioral symptoms persist after mammary tumor removal in mice (i.e., establishment of a cancer survivor model), while also empirically testing the causal role of tumors in the development of neuroinflammatory-mediated affective-like behaviors. Complete surgical resection of a non-metastatic orthotopic, syngeneic mammary tumor reversed tumor-induced increases of circulating cytokines (IL-6, CXCL1, IL-10) and myeloid-derived cells and modulated neuroinflammatory gene expression (Cd11b, Cxcl1). Multiple anxiety-like behaviors and some central and peripheral immune markers persisted or progressed three weeks after tumor resection. Together, these data indicate that persistent behavioral changes into cancer survivorhood may be due, in part, to changes in immunity that remain even after successful tumor removal. This novel survivor paradigm represents an improvement in modeling prevalent cancer survivorship issues and studying the basic mechanisms by which cancer/cancer treatments influence the brain and behavior.

KEYWORDS:

Corticosterone; Cytokines; MDSC; Mammary neoplasm; Tumor resection

PMID:
28479263
PMCID:
PMC5899888
DOI:
10.1016/j.bbr.2017.05.011
[Indexed for MEDLINE]
Free PMC Article

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