Enriched Environment Inhibits Mouse Pancreatic Cancer Growth and Down-regulates the Expression of Mitochondria-related Genes in Cancer Cells

Li, Guohua; Gan, Yu; Fan, Yingchao; Wu, Yufeng; Lin, Hechun; Song, Yanfang; Cai, Xiaojin; Yu, Xiang; Pan, Weihong; Yao, Ming; Gu, Jianren; Tu, Hong

doi:10.1038/srep07856

Cited by 55 publications

(59 citation statements)

References 60 publications

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“…Our previous studies show that metabolic changes are associated with the tumor resistance found after living in an EE (16). In particular, tumor growth is linked with higher β-AR activity in white adipose tissue leading to reduce circulating leptin concentrations (14).…”

Section: Discussionmentioning

confidence: 99%

“…In addition, an EE inhibits tumor progression in an implantation model of melanoma as well as a genetic model of colon cancer (14). Recent reports from others have shown the anticancer effects of an EE in orthotopic and spontaneous tumor models of breast, colon, pancreatic, and melanoma cancers (15, 16). We have identified one mechanism underlying the effects of an EE on metabolism and cancer, the activation of the hypothalamic-sympathoneural-adipocyte (HSA) axis (14).…”

Section: Introductionmentioning

confidence: 99%

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Environmental and Genetic Activation of Hypothalamic BDNF Modulates T-cell Immunity to Exert an Anticancer Phenotype

Xiao

Bergin

Huang

et al. 2016

Cancer Immunology Research

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Macro-environmental factors, including a patient’s physical and social environment, play a role in cancer risk and progression. Our previous studies show that living in an enriched environment (EE) providing complex stimuli confers an anticancer phenotype in mice mediated in part by a specific neuroendocrine axis, with brain-derived neurotrophic factor (BDNF) as the key brain mediator. Here we investigated how an EE modulated T-cell immunity and its role in the EE-induced anticancer effects. Our data demonstrated that CD8 T cells were required to mediate the anticancer effects of an EE in an orthotropic model of melanoma. In secondary lymphoid tissue (SLT), an EE induced early changes in the phenotype of T-cell populations, characterized by a decrease in the ratio of CD4 T helper to CD8 cytotoxic T lymphocytes (CTLs). Overexpression of hypothalamic BDNF reproduced EE-induced T-cell phenotypes in SLT whereas knockdown of hypothalamic BDNF inhibited EE-induced immune modulation in SLT. Both propranolol and mifepristone blocked the EE-associated modulation of CTLs in SLT suggesting both the sympathetic nervous system and hypothalamic-pituitary-adrenal axis were involved. Our results demonstrated that enhanced anticancer effect of an EE was mediated at least in part through modulation of T-cell immunity and provided support to the emerging concept of manipulating a single gene in the brain to improve cancer immunotherapy.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Environmental and Genetic Activation of Hypothalamic BDNF Modulates T-cell Immunity to Exert an Anticancer Phenotype

Xiao

Bergin

Huang

et al. 2016

Cancer Immunology Research

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“…Specifically, enrichment delayed onset of the cancer through a reduction in leptin levels. Enrichment consisting of inanimate objects, social stimulation and exercise was found to inhibit pancreatic cancer growth in both subcutaneous and orthotopic models . (p3) The same impact on BDNF was observed as had been reported by other laboratories, and it was observed that enrichment induced differential expression (downregulated) of genes, mostly located in the mitochondria of the tumors.…”

Section: Effects Of Enrichmentmentioning

confidence: 99%

Environmental enrichment and mouse models: Current perspectives

Bayne¹

2018

Anim Models and Exp Med

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The provision of environmental enrichment to numerous species of laboratory animals is generally considered routine husbandry. However, mouse enrichment has proven to be very complex due to the often contradictory outcomes (animal health and welfare, variability in scientific data, etc.) associated with strain, age of the animal when enrichment is provided, gender of the animal, scientific use of the animal, and other housing attributes. While this has led to some suggesting that mice should not be provided enrichment, more recently opinion is trending toward acknowledging that enrichment actually normalizes the animal and data obtained from a mouse living in a barren environment are likely not to be representative or even reliable. This article offers an overview of the types of impact enrichment can have on various strains of mice and demonstrates that enrichment not only has a role in mouse husbandry, but also can lead to new areas of scientific enquiry in a number of different fields. K E Y W O R D Sanimal welfare, environmental enrichment, mouse behavior, research validity | INTRODUCTIONThe laboratory mouse is a ubiquitously used research subject whose genetics, anatomy, physiology, immunology, and behavior have been studied in detail for generations. Thus, it would seem that providing a housing environment that is species-appropriate would be a simple matter. However, it would be a serious mistake to approach mouse enrichment as a one-size-fits-all husbandry procedure. The laboratory mouse is still considered behaviorally similar to wild mice in many dimensions 1(p150) , though it differs somewhat from the wildtype ancestor in its behavior, with running behavior and open-field freezing behavior, and a general higher level of activity more evident in wild-type mice than the laboratory bred animals.2 Over decades of purposeful breeding, a variety of characteristics (eg, ease of handling) were either deliberately or inadvertently introduced into the behavior profile of the laboratory mouse. Today, the increasing trend in the use of transgenic mice has only amplified the diversity of traits being bred for, and thus, the potential exists for both extant and subtle differences in mouse behavior and their response to their environment.The behavioral breadth of the species may help to account for the fact that the literature is replete with contradictory findings and diverse conclusions about the potential benefits and unexpected consequences from providing enrichment to laboratory mice.Indeed, an argument has been made that enriched animals produce different results; enrichment may increase between-subject variability; and enrichment may reduce replicability across laboratories. 3(p47-48) A simple response to these arguments could be that animals should not be provided enrichment. But, a counter-argument has been made that, as expected, the enriched animal model is different in many ways from the animal model living in a barren environment. 3(p47) Indeed, it is not logical to accept the notion that --

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“…Reports from others confirm the anticancer effects of an EE in breast and pancreatic cancers [4,5]. Our previous studies have uncovered one underlying mechanism, the activation of a specific neuroendocrine axis: the Hypothalamic-Sympathoneural-Adipocyte (HSA) axis.…”

Section: Editorialmentioning

confidence: 73%

Anticancer Molecules in Brain: Implication for Novel Strategy for Cancer Immunotherapy

Xiao

Bergin

Zhang

et al. 2016

Immunother Open Acc

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Enriched Environment Inhibits Mouse Pancreatic Cancer Growth and Down-regulates the Expression of Mitochondria-related Genes in Cancer Cells

Cited by 55 publications

References 60 publications

Environmental and Genetic Activation of Hypothalamic BDNF Modulates T-cell Immunity to Exert an Anticancer Phenotype

Environmental and Genetic Activation of Hypothalamic BDNF Modulates T-cell Immunity to Exert an Anticancer Phenotype

Environmental enrichment and mouse models: Current perspectives

Anticancer Molecules in Brain: Implication for Novel Strategy for Cancer Immunotherapy

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