PMID- 16141784
OWN - NLM
STAT- MEDLINE
DCOM- 20051012
LR  - 20210102
IS  - 0022-3069 (Print)
IS  - 0022-3069 (Linking)
VI  - 64
IP  - 9
DP  - 2005 Sep
TI  - Microglia stimulate the invasiveness of glioma cells by increasing the activity 
      of metalloprotease-2.
PG  - 754-62
AB  - Gliomas represent the most frequent type of human brain tumor, and their strong 
      invasiveness is a significant clinical problem. Microglia, the immunocompetent 
      cells of the brain, contribute significantly to the tumor and are potential 
      interaction partners of the glioma cells. We studied the impact of the presence 
      of microglia on tumor cell invasion in cultured brain slices. To selectively 
      deplete microglia, the slices were treated with clodronate-filled liposomes. When 
      glioma cells were injected into slices devoid of endogenous microglia, the 
      invasiveness of the tumors was significantly decreased as compared with controls. 
      Inoculation of exogenous microglia together with glioma cells into cultured brain 
      slices increased the infiltrative behavior of the tumor depending on the 
      microglia/glioma cell ratio. Cell culture experiments revealed that soluble 
      factors released from glioma cells strongly stimulate metalloprotease-2 activity 
      in microglia. In the brain slices inoculated with glioma cells, increased 
      activity of metalloprotease-2 was directly correlated with the abundance of 
      microglia. Our data indicate that glioma cells stimulate microglial cells to 
      increase breakdown of extracellular matrix and thereby promote tumor 
      invasiveness.
FAU - Markovic, Darko S
AU  - Markovic DS
AD  - Cellular Neuroscience Group, Max Delbruck Center for Molecular Medicine (MDC), 
      Berlin, Germany.
FAU - Glass, Rainer
AU  - Glass R
FAU - Synowitz, Michael
AU  - Synowitz M
FAU - Rooijen, Nico van
AU  - Rooijen Nv
FAU - Kettenmann, Helmut
AU  - Kettenmann H
LA  - eng
PT  - Journal Article
PL  - England
TA  - J Neuropathol Exp Neurol
JT  - Journal of neuropathology and experimental neurology
JID - 2985192R
RN  - 0 (Antimetabolites)
RN  - 0 (Liposomes)
RN  - 0813BZ6866 (Clodronic Acid)
RN  - EC 3.4.- (Metalloproteases)
SB  - IM
MH  - Animals
MH  - Antimetabolites/administration & dosage
MH  - Brain Neoplasms/metabolism/*pathology
MH  - Cell Line, Tumor
MH  - Clodronic Acid/administration & dosage
MH  - Fluorescent Antibody Technique
MH  - Glioma/metabolism/*pathology
MH  - Humans
MH  - Liposomes
MH  - Male
MH  - Metalloproteases/*metabolism
MH  - Mice
MH  - Microglia/drug effects/*enzymology
MH  - Microscopy, Confocal
MH  - Neoplasm Invasiveness/*pathology
MH  - Organ Culture Techniques
EDAT- 2005/09/06 09:00
MHDA- 2005/10/13 09:00
CRDT- 2005/09/06 09:00
PHST- 2005/09/06 09:00 [pubmed]
PHST- 2005/10/13 09:00 [medline]
PHST- 2005/09/06 09:00 [entrez]
AID - 00005072-200509000-00002 [pii]
AID - 10.1097/01.jnen.0000178445.33972.a9 [doi]
PST - ppublish
SO  - J Neuropathol Exp Neurol. 2005 Sep;64(9):754-62. doi: 
      10.1097/01.jnen.0000178445.33972.a9.