The role of microglia, the brain-resident macrophages, in glioma biology is still a matter of debate. Clinical observations and in vitro studies in the mouse model indicate that microglia and macrophages that infiltrate the brain tumor tissue in high numbers play a tumorsupportive role. Here, we provide evidence that human microglia isolated from brain tumors indeed support tumor cell growth, migration, and invasion. However, after stimulation with the Toll-like receptor 3 agonist poly (I:C), microglia secrete factors that exerted toxic and suppressive effects on different glioblastoma cell lines, as assessed in cytotoxicity, migration, and tumor cell spheroid invasion assays. Remarkably, these effects were tumor-specific because the microglial factors impaired neither growth nor viability of astrocytes and neurons. Culture supernatants of tumor cells inhibited the poly (I:C) induction of this microglial M1-like, oncotoxic profile. Microglia stimulation before coculture with tumor cells circumvented the tumor-mediated suppression, as demonstrated by the ability to kill and phagocytose glioma cells. Our results show, for the first time to our knowledge, that human microglia exert tumor-supporting functions that are overridden by tumor-suppressing activities gained after poly (I:C) stimulation.
Insular glioma combined treatment : a retrospective analysis of 50 consecutive patients / M. Riva, F. Raneri, F. Pessina, A. Casarotti, A. Comi, E. Fava, C. Papagno, L. Bello. - In: NEURO-ONCOLOGY. - ISSN 1522-8517. - 14:suppl. 3(2012 Sep), pp. 64-64. ((Intervento presentato al 10. convegno Congress of the European Association of NeuroOncology tenutosi a Marseille nel 2012.
|Titolo:||Insular glioma combined treatment : a retrospective analysis of 50 consecutive patients|
RIVA, MARCO (Primo)
RANERI, FABIO ANGELO (Secondo)
BELLO, LORENZO (Ultimo)
|Parole Chiave:||Antitumor response; Glioma; Human microglia; Poly (I:C)|
|Settore Scientifico Disciplinare:||Settore MED/27 - Neurochirurgia|
Settore MED/26 - Neurologia
|Data di pubblicazione:||set-2012|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1093/neuonc/nos183|
|Appare nelle tipologie:||01 - Articolo su periodico|