Vitamin D and VDR in cancer cachexia and muscle regeneration

Andrea Camperi, Fabrizio Pin, Domiziana Costamagna, Fabio Penna, Maria Lopez Menduina, Zaira Aversa, Teresa Zimmers, Roberto Verzaro, Raffaella Fittipaldi, Giuseppina Caretti, Francesco Maria Baccino, Maurizio Muscaritoli, Paola Costelli

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Low circulating levels of vitamin D were associated with decreased muscle strength and physical performance. Along this line, the present study was aimed to investigate: i) the therapeutic potential of vitamin D in cancer-induced muscle wasting; ii) the mechanisms by which vitamin D affects muscle phenotype in tumorbearing animals. Rats bearing the AH130 hepatoma showed decreased circulating vitamin D compared to control rats, while muscle vitamin D receptor (VDR) mRNA was upregulated. Both circulating vitamin D and muscle VDR expression increased after vitamin D administration, without exerting appreciable effects on body weight and muscle mass. The effects of vitamin D on muscle cells were studied in C2C12 myocytes. Vitamin D-treated myoblasts did not differentiate properly, fusing only partially and forming multinucleated structures with aberrant shape and low myosin heavy chain content. Vitamin D treatment resulted in VDR overexpression and myogenin down-regulation. Silencing VDR expression in C2C12 cultures abrogated the inhibition of differentiation exerted by vitamin D treatment. These data suggest that VDR overexpression in tumor-bearing animals contributes to muscle wasting by impairing muscle regenerative program. In this regard, attention should be paid when considering vitamin D supplementation to patients affected by chronic pathologies where muscle regeneration may be involved.

Original languageEnglish (US)
Pages (from-to)21778-21793
Number of pages16
JournalOncotarget
Volume8
Issue number13
DOIs
StatePublished - Jan 1 2017

Keywords

  • Circulating vitamin D
  • Muscle wasting
  • Myogenin
  • Regeneration
  • Vitamin D receptor

ASJC Scopus subject areas

  • Oncology

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  • Cite this

    Camperi, A., Pin, F., Costamagna, D., Penna, F., Menduina, M. L., Aversa, Z., Zimmers, T., Verzaro, R., Fittipaldi, R., Caretti, G., Baccino, F. M., Muscaritoli, M., & Costelli, P. (2017). Vitamin D and VDR in cancer cachexia and muscle regeneration. Oncotarget, 8(13), 21778-21793. https://doi.org/10.18632/oncotarget.15583