Enriched environment reduces glioma growth through immune and non-immune mechanisms in mice

Stefano Garofalo, Giuseppina D'Alessandro, Giuseppina Chece, Frederic Brau, Laura Maggi, Alessandro Rosa, Alessandra Porzia, Fabrizio Mainiero, Vincenzo Esposito, Clotilde Lauro, Giorgia Benigni, Giovanni Bernardini, Angela Santoni, Cristina Limatola

Research output: Contribution to journalArticle

Abstract

Mice exposed to standard (SE) or enriched environment (EE) were transplanted with murine or human glioma cells and differences in tumour development were evaluated. We report that EE exposure affects: (i) tumour size, increasing mice survival; (ii) glioma establishment, proliferation and invasion; (iii) microglia/macrophage (M/M) activation; (iv) natural killer (NK) cell infiltration and activation; and (v) cerebral levels of IL-15 and BDNF. Direct infusion of IL-15 or BDNF in the brain of mice transplanted with glioma significantly reduces tumour growth. We demonstrate that brain infusion of IL-15 increases the frequency of NK cell infiltrating the tumour and that NK cell depletion reduces the efficacy of EE and IL-15 on tumour size and of EE on mice survival. BDNF infusion reduces M/M infiltration and CD68 immunoreactivity in tumour mass and reduces glioma migration inhibiting the small G protein RhoA through the truncated TrkB.T1 receptor. These results suggest alternative approaches for glioma treatment.

Original languageEnglish
Article number6623
JournalNature Communications
Volume6
DOIs
Publication statusPublished - 2015

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Chemistry(all)
  • Physics and Astronomy(all)

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    Garofalo, S., D'Alessandro, G., Chece, G., Brau, F., Maggi, L., Rosa, A., Porzia, A., Mainiero, F., Esposito, V., Lauro, C., Benigni, G., Bernardini, G., Santoni, A., & Limatola, C. (2015). Enriched environment reduces glioma growth through immune and non-immune mechanisms in mice. Nature Communications, 6, [6623]. https://doi.org/10.1038/ncomms7623