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

Fingerprint

Glioma
mice
Tumors
Interleukin-15
tumors
Brain-Derived Neurotrophic Factor
Growth
Natural Killer Cells
Neoplasms
macrophages
Macrophages
Microglia
infiltration
cells
Infiltration
brain
Brain
Chemical activation
activation
Monomeric GTP-Binding Proteins

ASJC Scopus subject areas

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

Cite this

Enriched environment reduces glioma growth through immune and non-immune mechanisms in mice. / Garofalo, Stefano; D'Alessandro, Giuseppina; Chece, Giuseppina; Brau, Frederic; Maggi, Laura; Rosa, Alessandro; Porzia, Alessandra; Mainiero, Fabrizio; Esposito, Vincenzo; Lauro, Clotilde; Benigni, Giorgia; Bernardini, Giovanni; Santoni, Angela; Limatola, Cristina.

In: Nature Communications, Vol. 6, 6623, 2015.

Research output: Contribution to journalArticle

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, vol. 6, 6623. https://doi.org/10.1038/ncomms7623
Garofalo, Stefano ; D'Alessandro, Giuseppina ; Chece, Giuseppina ; Brau, Frederic ; Maggi, Laura ; Rosa, Alessandro ; Porzia, Alessandra ; Mainiero, Fabrizio ; Esposito, Vincenzo ; Lauro, Clotilde ; Benigni, Giorgia ; Bernardini, Giovanni ; Santoni, Angela ; Limatola, Cristina. / Enriched environment reduces glioma growth through immune and non-immune mechanisms in mice. In: Nature Communications. 2015 ; Vol. 6.
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AU - Rosa, Alessandro

AU - Porzia, Alessandra

AU - Mainiero, Fabrizio

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