PMID- 21901144
OWN - NLM
STAT- MEDLINE
DCOM- 20120413
LR  - 20220408
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 6
IP  - 8
DP  - 2011
TI  - Characteristics of the alternative phenotype of microglia/macrophages and its 
      modulation in experimental gliomas.
PG  - e23902
LID - 10.1371/journal.pone.0023902 [doi]
LID - e23902
AB  - Microglia (brain resident macrophages) accumulate in malignant gliomas and 
      instead of initiating the anti-tumor response, they switch to a pro-invasive 
      phenotype, support tumor growth, invasion, angiogenesis and immunosuppression by 
      release of cytokines/chemokines and extracellular matrix proteases. Using 
      immunofluorescence and flow cytometry, we demonstrate an early accumulation of 
      activated microglia followed by accumulation of macrophages in experimental 
      murine EGFP-GL261 gliomas. Those cells acquire the alternative phenotype, as 
      evidenced by evaluation of the production of ten pro/anti-inflammatory cytokines 
      and expression profiling of 28 genes in magnetically-sorted CD11b(+) cells from 
      tumor tissues. Furthermore, we show that infiltration of implanted gliomas by 
      amoeboid, Iba1-positive cells can be reduced by a systematically injected 
      cyclosporine A (CsA) two or eight days after cell inoculation. The up-regulated 
      levels of IL-10 and GM-CSF, increased expression of genes characteristic for the 
      alternative and pro-invasive phenotype (arg-1, mt1-mmp, cxcl14) in glioma-derived 
      CD11b(+) cells as well as enhanced angiogenesis and tumor growth were reduced in 
      CsA-treated mice. Our findings define for the first time kinetics and biochemical 
      characteristics of glioma-infiltrating microglia/macrophages. Inhibition of the 
      alternative activation of tumor-infiltrating macrophages significantly reduced 
      tumor growth. Thus, blockade of microglia/macrophage infiltration and their 
      pro-invasive functions could be a novel therapeutic strategy in malignant 
      gliomas.
FAU - Gabrusiewicz, Konrad
AU  - Gabrusiewicz K
AD  - Laboratory of Transcription Regulation, Nencki Institute of Experimental Biology, 
      Warsaw, Poland.
FAU - Ellert-Miklaszewska, Aleksandra
AU  - Ellert-Miklaszewska A
FAU - Lipko, Maciej
AU  - Lipko M
FAU - Sielska, Malgorzata
AU  - Sielska M
FAU - Frankowska, Marta
AU  - Frankowska M
FAU - Kaminska, Bozena
AU  - Kaminska B
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110825
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (CD11b Antigen)
RN  - 0 (CXCL14 protein, mouse)
RN  - 0 (Chemokines, CXC)
RN  - 0 (Mmp14 protein, mouse)
RN  - 130068-27-8 (Interleukin-10)
RN  - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor)
RN  - EC 3.4.24.24 (Matrix Metalloproteinase 2)
RN  - EC 3.4.24.80 (Matrix Metalloproteinase 14)
SB  - IM
MH  - Animals
MH  - Brain/metabolism
MH  - CD11b Antigen/metabolism
MH  - Cell Line, Tumor
MH  - Cells, Cultured
MH  - Chemokines, CXC/metabolism
MH  - Flow Cytometry
MH  - Fluorescent Antibody Technique
MH  - Glioma/*metabolism/*pathology
MH  - Granulocyte-Macrophage Colony-Stimulating Factor/metabolism
MH  - Immunohistochemistry
MH  - Interleukin-10/metabolism
MH  - Macrophages/metabolism/*pathology
MH  - Male
MH  - Matrix Metalloproteinase 14/metabolism
MH  - Matrix Metalloproteinase 2/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Microglia/metabolism/*pathology
PMC - PMC3162015
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2011/09/09 06:00
MHDA- 2012/04/14 06:00
PMCR- 2011/08/25
CRDT- 2011/09/09 06:00
PHST- 2011/05/24 00:00 [received]
PHST- 2011/07/27 00:00 [accepted]
PHST- 2011/09/09 06:00 [entrez]
PHST- 2011/09/09 06:00 [pubmed]
PHST- 2012/04/14 06:00 [medline]
PHST- 2011/08/25 00:00 [pmc-release]
AID - PONE-D-11-09230 [pii]
AID - 10.1371/journal.pone.0023902 [doi]
PST - ppublish
SO  - PLoS One. 2011;6(8):e23902. doi: 10.1371/journal.pone.0023902. Epub 2011 Aug 25.