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Quantitative proteomic analysis of murine white adipose tissue for peritoneal cancer metastasis

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Abstract

Cancer metastasis risk increases in older individuals, but the mechanisms for this risk increase are unclear. Many peritoneal cancers, including ovarian cancer, preferentially metastasize to peritoneal fat depots. However, there is a dearth of studies exploring aged peritoneal adipose tissue in the context of cancer. Because adipose tissue produces signals which influence several diseases including cancer, proteomics of adipose tissue in aged and young mice may provide insight into metastatic mechanisms. We analyzed mesenteric, omental, and uterine adipose tissue groups from the peritoneal cavities of young and aged C57BL/6J mouse cohorts with a low-fraction SDS-PAGE gelLC-MS/MS method. We identified 2308 protein groups and quantified 2167 groups, among which several protein groups showed twofold or greater abundance differences between the aged and young cohorts. Cancer-related gene products previously identified as significant in another age-related study were found altered in this study. Several gene products known to suppress proliferation and cellular invasion were found downregulated in the aged cohort, including R-Ras, Arid1a, and heat shock protein β1. In addition, multiple protein groups were identified within single cohorts, including the proteins Cd11a, Stat3, and Ptk2b. These data suggest that adipose tissue is a strong candidate for analysis to identify possible contributors to cancer metastasis in older subjects. The results of this study, the first of its kind using uterine adipose tissue, contribute to the understanding of the role of adipose tissue in age-related alteration of oncogenic pathways, which may help elucidate the mechanisms of increased metastatic tumor burden in the aged.

We analyzed mesenteric, omental, and uterine adipose tissue groups from the peritoneal cavities of young and aged C57BL/6J mouse cohorts with a low-fraction SDS-PAGE gelLC-MS/MS method. These fat depots are preferential sites for many peritoneal cancers. The results of this study, the first of its kind using uterine adipose tissue, contribute to the understanding of the role of adipose tissue in age-related alteration of oncogenic pathways, which may help elucidate the mechanisms of increased metastatic tumor burden in the aged.

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Acknowledgements

We gratefully acknowledge the assistance of the Notre Dame Mass Spectrometry and Proteomics Facility (MSPF).

Funding

PF was supported by an Arthur J. Schmitt Presidential Fellowship. ABH was supported by the National Institutes of Health (R01GM110406) and the National Science Foundation (CAREER Award, CHE-1351595). EAL was supported by a National Science Foundation Graduate Research Fellowship Program grant DGE-1313583. MSS is supported by the National Institutes of Health (RO1CA109545) and the Leo and Anne Albert Charitable Trust.

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Correspondence to Amanda B. Hummon.

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This research includes animal research. All mouse procedures were carried out according to the regulations of the University of Notre Dame Animal Care and Use Committee (IACUC 14-02-1577) and with approval of the Notre Dame Institutional Review Board.

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The authors declare that they have no conflicts of interest.

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Feist, P.E., Loughran, E.A., Stack, M.S. et al. Quantitative proteomic analysis of murine white adipose tissue for peritoneal cancer metastasis. Anal Bioanal Chem 410, 1583–1594 (2018). https://doi.org/10.1007/s00216-017-0813-9

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