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Proteomic profiling of the hypothalamus in a mouse model of cancer-induced anorexia-cachexia
Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences.ORCID iD: 0000-0001-5751-3622
Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences.
2013 (English)In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 109, no 7, 1867-1875 p.Article in journal (Refereed) Published
Abstract [en]

Background:

Anorexia-cachexia is a common and severe cancer-related complication but the underlying mechanisms are largely unknown. Here, using a mouse model for tumour-induced anorexia-cachexia, we screened for proteins that are differentially expressed in the hypothalamus, the brain’s metabolic control centre.

Methods:

The hypothalamus of tumour-bearing mice with implanted methylcholanthrene-induced sarcoma (MCG 101) displaying anorexia and their sham-implanted pair-fed or free-fed littermates was examined using two-dimensional electrophoresis (2-DE)-based comparative proteomics. Differentially expressed proteins were identified by liquid chromatography-tandem mass spectrometry.

Results:

The 2-DE data showed an increased expression of dynamin 1, hexokinase, pyruvate carboxylase, oxoglutarate dehydrogenase, and N-ethylmaleimide-sensitive factor in tumour-bearing mice, whereas heat-shock 70 kDa cognate protein, selenium-binding protein 1, and guanine nucleotide-binding protein Gα0 were downregulated. The expression of several of the identified proteins was similarly altered also in the caloric-restricted pair-fed mice, suggesting an involvement of these proteins in brain metabolic adaptation to restricted nutrient availability. However, the expression of dynamin 1, which is required for receptor internalisation, and of hexokinase, and pyruvate carboxylase were specifically changed in tumour-bearing mice with anorexia.

Conclusion:

The identified differentially expressed proteins may be new candidate molecules involved in the pathophysiology of tumour-induced anorexia-cachexia.

Place, publisher, year, edition, pages
Cancer Research UK , 2013. Vol. 109, no 7, 1867-1875 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-100305DOI: 10.1038/bjc.2013.525ISI: 000325216700021OAI: oai:DiVA.org:liu-100305DiVA: diva2:661514
Note

Funding Agencies|Swedish Cancer Foundation|12 0553|Swedish Research Council|12X-07879|

Available from: 2013-11-04 Created: 2013-11-04 Last updated: 2017-12-06Bibliographically approved

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