Chronic social isolation is associated with metabolic gene expression changes specific to mammary adipose tissue

Paul A. Volden, Erin L. Wonder, Maxwell N. Skor, Christopher M. Carmean, Feenalie N. Patel, Honggang Ye, Masha Kocherginsky, Martha K. McClintock, Matthew J. Brady, Suzanne D. Conzen

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Chronic social isolation is linked to increased mammary tumor growth in rodent models of breast cancer. In the C3(1)/SV40 T-antigen FVB/N (TAg) mouse model of "triple-negative" breast cancer, the heightened stress response elicited by social isolation has been associated with increased expression of metabolic genes in the mammary gland before invasive tumors develop (i.e., during the in situ carcinoma stage). To further understand the mechanisms underlying how accelerated mammary tumor growth is associated with social isolation, we separated the mammary gland adipose tissue from adjacent ductal epithelial cells and analyzed individual cell types for changes in metabolic gene expression. Specifically, increased expression of the key metabolic genes Acaca, Hk2, and Acly was found in the adipocyte, rather than the epithelial fraction. Surprisingly, metabolic gene expression was not significantly increased in visceral adipose depots of socially isolated female mice. As expected, increased metabolic gene expression in the mammary adipocytes of socially isolated mice coincided with increased glucose metabolism, lipid synthesis, and leptin secretion from this adipose depot. Furthermore, application of media that had been cultured with isolated mouse mammary adipose tissue (conditioned media) resulted in increased proliferation of mammary cancer cells relative to group-housed-conditioned media. These results suggest that exposure to a chronic stressor (social isolation) results in specific metabolic reprogramming in mammary gland adipocytes that in turn contributes to increased proliferation of adjacent preinvasive malignant epithelial cells. Metabolites and/or tumor growth-promoting proteins secreted from adipose tissue could identify biomarkers and/or targets for preventive intervention in breast cancer.

Original languageEnglish (US)
Pages (from-to)634-645
Number of pages12
JournalCancer Prevention Research
Volume6
Issue number7
DOIs
StatePublished - Jul 1 2013

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Social Isolation
Adipose Tissue
Breast
Breast Neoplasms
Gene Expression
Human Mammary Glands
Adipocytes
Conditioned Culture Medium
Growth
Epithelial Cells
Triple Negative Breast Neoplasms
Polyomavirus Transforming Antigens
Carcinoma in Situ
Leptin
Lipid Metabolism
Rodentia
Neoplasms
Biomarkers
Glucose
Genes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Volden, P. A., Wonder, E. L., Skor, M. N., Carmean, C. M., Patel, F. N., Ye, H., ... Conzen, S. D. (2013). Chronic social isolation is associated with metabolic gene expression changes specific to mammary adipose tissue. Cancer Prevention Research, 6(7), 634-645. https://doi.org/10.1158/1940-6207.CAPR-12-0458
Volden, Paul A. ; Wonder, Erin L. ; Skor, Maxwell N. ; Carmean, Christopher M. ; Patel, Feenalie N. ; Ye, Honggang ; Kocherginsky, Masha ; McClintock, Martha K. ; Brady, Matthew J. ; Conzen, Suzanne D. / Chronic social isolation is associated with metabolic gene expression changes specific to mammary adipose tissue. In: Cancer Prevention Research. 2013 ; Vol. 6, No. 7. pp. 634-645.
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Volden, PA, Wonder, EL, Skor, MN, Carmean, CM, Patel, FN, Ye, H, Kocherginsky, M, McClintock, MK, Brady, MJ & Conzen, SD 2013, 'Chronic social isolation is associated with metabolic gene expression changes specific to mammary adipose tissue', Cancer Prevention Research, vol. 6, no. 7, pp. 634-645. https://doi.org/10.1158/1940-6207.CAPR-12-0458

Chronic social isolation is associated with metabolic gene expression changes specific to mammary adipose tissue. / Volden, Paul A.; Wonder, Erin L.; Skor, Maxwell N.; Carmean, Christopher M.; Patel, Feenalie N.; Ye, Honggang; Kocherginsky, Masha; McClintock, Martha K.; Brady, Matthew J.; Conzen, Suzanne D.

In: Cancer Prevention Research, Vol. 6, No. 7, 01.07.2013, p. 634-645.

Research output: Contribution to journalArticle

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T1 - Chronic social isolation is associated with metabolic gene expression changes specific to mammary adipose tissue

AU - Volden, Paul A.

AU - Wonder, Erin L.

AU - Skor, Maxwell N.

AU - Carmean, Christopher M.

AU - Patel, Feenalie N.

AU - Ye, Honggang

AU - Kocherginsky, Masha

AU - McClintock, Martha K.

AU - Brady, Matthew J.

AU - Conzen, Suzanne D.

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Y1 - 2013/7/1

N2 - Chronic social isolation is linked to increased mammary tumor growth in rodent models of breast cancer. In the C3(1)/SV40 T-antigen FVB/N (TAg) mouse model of "triple-negative" breast cancer, the heightened stress response elicited by social isolation has been associated with increased expression of metabolic genes in the mammary gland before invasive tumors develop (i.e., during the in situ carcinoma stage). To further understand the mechanisms underlying how accelerated mammary tumor growth is associated with social isolation, we separated the mammary gland adipose tissue from adjacent ductal epithelial cells and analyzed individual cell types for changes in metabolic gene expression. Specifically, increased expression of the key metabolic genes Acaca, Hk2, and Acly was found in the adipocyte, rather than the epithelial fraction. Surprisingly, metabolic gene expression was not significantly increased in visceral adipose depots of socially isolated female mice. As expected, increased metabolic gene expression in the mammary adipocytes of socially isolated mice coincided with increased glucose metabolism, lipid synthesis, and leptin secretion from this adipose depot. Furthermore, application of media that had been cultured with isolated mouse mammary adipose tissue (conditioned media) resulted in increased proliferation of mammary cancer cells relative to group-housed-conditioned media. These results suggest that exposure to a chronic stressor (social isolation) results in specific metabolic reprogramming in mammary gland adipocytes that in turn contributes to increased proliferation of adjacent preinvasive malignant epithelial cells. Metabolites and/or tumor growth-promoting proteins secreted from adipose tissue could identify biomarkers and/or targets for preventive intervention in breast cancer.

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