Microglia isolated from patients with glioma gain antitumor activities on poly (I:C) stimulation
| Autor: | Johannes Noack, Rodrigo Mora, Georg Gdynia, Bernhard Radlwimmer, Grischa Tödt, Christel Herold-Mende, Aurélie Ernst, Christine S. Falk, Jennifer Lohr, Tim Kees, Anne Régnier-Vigouroux |
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| Rok vydání: | 2011 |
| Předmět: |
Cancer Research
Antineoplastic Agents Stimulation Biology Cell Movement Cell Line Tumor Glioma medicine Humans Macrophage Neoplasm Invasiveness Cytotoxicity Cells Cultured Cell Proliferation Microglia Brain Neoplasms Cell growth medicine.disease Coculture Techniques In vitro Toll-Like Receptor 3 Poly I-C medicine.anatomical_structure Oncology Cell culture Basic and Translational Investigations Immunology Cancer research Neurology (clinical) |
| Zdroj: | Neuro-Oncology. 14:64-78 |
| ISSN: | 1523-5866 1522-8517 |
| DOI: | 10.1093/neuonc/nor182 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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