PMID- 22015597
OWN - NLM
STAT- MEDLINE
DCOM- 20120412
LR  - 20220223
IS  - 1523-5866 (Electronic)
IS  - 1522-8517 (Print)
IS  - 1522-8517 (Linking)
VI  - 14
IP  - 1
DP  - 2012 Jan
TI  - Microglia isolated from patients with glioma gain antitumor activities on poly 
      (I:C) stimulation.
PG  - 64-78
LID - 10.1093/neuonc/nor182 [doi]
AB  - 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.
FAU - Kees, Tim
AU  - Kees T
AD  - INSERM U701, German Cancer Research Centre, INF 242, Germany.
FAU - Lohr, Jennifer
AU  - Lohr J
FAU - Noack, Johannes
AU  - Noack J
FAU - Mora, Rodrigo
AU  - Mora R
FAU - Gdynia, Georg
AU  - Gdynia G
FAU - Todt, Grischa
AU  - Todt G
FAU - Ernst, Aurelie
AU  - Ernst A
FAU - Radlwimmer, Bernhard
AU  - Radlwimmer B
FAU - Falk, Christine S
AU  - Falk CS
FAU - Herold-Mende, Christel
AU  - Herold-Mende C
FAU - Regnier-Vigouroux, Anne
AU  - Regnier-Vigouroux A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20111020
PL  - England
TA  - Neuro Oncol
JT  - Neuro-oncology
JID - 100887420
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Toll-Like Receptor 3)
RN  - O84C90HH2L (Poly I-C)
SB  - IM
MH  - Antineoplastic Agents/*pharmacology
MH  - Brain Neoplasms/*metabolism
MH  - Cell Line, Tumor
MH  - Cell Movement
MH  - Cell Proliferation
MH  - Cells, Cultured
MH  - Coculture Techniques
MH  - Glioma/*metabolism
MH  - Humans
MH  - Microglia/drug effects/*physiology
MH  - Neoplasm Invasiveness
MH  - Poly I-C/*pharmacology
MH  - Toll-Like Receptor 3/*agonists
PMC - PMC3245995
EDAT- 2011/10/22 06:00
MHDA- 2012/04/13 06:00
PMCR- 2013/01/01
CRDT- 2011/10/22 06:00
PHST- 2011/10/22 06:00 [entrez]
PHST- 2011/10/22 06:00 [pubmed]
PHST- 2012/04/13 06:00 [medline]
PHST- 2013/01/01 00:00 [pmc-release]
AID - nor182 [pii]
AID - 10.1093/neuonc/nor182 [doi]
PST - ppublish
SO  - Neuro Oncol. 2012 Jan;14(1):64-78. doi: 10.1093/neuonc/nor182. Epub 2011 Oct 20.