Neuro-oncology (Charlottesville, Va.), 2012-01, Vol.14 (1), p.64-78
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 tumor-supportive 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.
Poly I-C - pharmacology ; Cell Proliferation ; Microglia - drug effects ; Neoplasm Invasiveness ; Coculture Techniques ; Humans ; Cells, Cultured ; Toll-Like Receptor 3 - agonists ; Brain Neoplasms - metabolism ; Glioma - metabolism ; Microglia - physiology ; Cell Line, Tumor ; Antineoplastic Agents - pharmacology ; Cell Movement ; glioma ; poly (I:C) ; Basic and Translational Investigations ; antitumor response ; human microglia
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