Cardiac and skeletal muscles show molecularly distinct responses to cancer cachexia.

Autor:	Shum AM; Inflammation and Infection Research Centre, University of New South Wales Australia, New South Wales, Australia; Department of Pathology, School of Medical Sciences, Faculty of Medicine, University of New South Wales Australia, New South Wales, Australia;, Fung DC; School of Biotechnology and Biomolecular Sciences, Faculty of Science, University of New South Wales Australia, New South Wales, Australia;, Corley SM; New South Wales Systems Biology Initiative, University of New South Wales Australia, New South Wales, Australia; School of Biotechnology and Biomolecular Sciences, Faculty of Science, University of New South Wales Australia, New South Wales, Australia;, McGill MC; Inflammation and Infection Research Centre, University of New South Wales Australia, New South Wales, Australia; Department of Pathology, School of Medical Sciences, Faculty of Medicine, University of New South Wales Australia, New South Wales, Australia;, Bentley NL; Inflammation and Infection Research Centre, University of New South Wales Australia, New South Wales, Australia; Mitochondrial Bioenergetics Group, Department of Pharmacology, School of Medical Sciences, Faculty of Medicine, University of New South Wales Australia, New South Wales, Australia;, Tan TC; Inflammation and Infection Research Centre, University of New South Wales Australia, New South Wales, Australia; Blacktown Clinical School and Blacktown Hospital, Blacktown, New South Wales, Australia; and Cardiac Ultrasound Laboratory, Massachusetts General Hospital, Boston, Massachusetts., Wilkins MR; New South Wales Systems Biology Initiative, University of New South Wales Australia, New South Wales, Australia; School of Biotechnology and Biomolecular Sciences, Faculty of Science, University of New South Wales Australia, New South Wales, Australia;, Polly P; Inflammation and Infection Research Centre, University of New South Wales Australia, New South Wales, Australia; Department of Pathology, School of Medical Sciences, Faculty of Medicine, University of New South Wales Australia, New South Wales, Australia; patsie.polly@unsw.edu.au.
Jazyk:	angličtina
Zdroj:	Physiological genomics [Physiol Genomics] 2015 Dec; Vol. 47 (12), pp. 588-99. Date of Electronic Publication: 2015 Sep 22.
DOI:	10.1152/physiolgenomics.00128.2014
Abstrakt:	Cancer cachexia is a systemic, paraneoplastic syndrome seen in patients with advanced cancer. There is growing interest in the altered muscle pathophysiology experienced by cachectic patients. This study reports the microarray analysis of gene expression in cardiac and skeletal muscle in the colon 26 (C26) carcinoma mouse model of cancer cachexia. A total of 268 genes were found to be differentially expressed in cardiac muscle tissue, compared with nontumor-bearing controls. This was fewer than the 1,533 genes that changed in cachectic skeletal muscle. In addition to different numbers of genes changing, different cellular functions were seen to change in each tissue. The cachectic heart showed signs of inflammation, similar to cachectic skeletal muscle, but did not show the upregulation of ubiquitin-dependent protein catabolic processes or downregulation of genes involved in cellular energetics and muscle regeneration that characterizes skeletal muscle cachexia. Quantitative PCR was used to investigate a subset of inflammatory genes in the cardiac and skeletal muscle of independent cachectic samples; this revealed that B4galt1, C1s, Serpina3n, and Vsig4 were significantly upregulated in cardiac tissue, whereas C1s and Serpina3n were significantly upregulated in skeletal tissue. Our skeletal muscle microarray results were also compared with those from three published microarray studies and found to be consistent in terms of the genes differentially expressed and the functional processes affected. Our study highlights that skeletal and cardiac muscles are affected differently in the C26 mouse model of cachexia and that therapeutic strategies cannot assume that both muscle types will show a similar response. (Copyright © 2015 the American Physiological Society.)
Databáze:	MEDLINE
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