PMID- 22294205
OWN - NLM
STAT- MEDLINE
DCOM- 20120904
LR  - 20220408
IS  - 1528-3658 (Electronic)
IS  - 1076-1551 (Print)
IS  - 1076-1551 (Linking)
VI  - 18
IP  - 1
DP  - 2012 May 9
TI  - Microglial stimulation of glioblastoma invasion involves epidermal growth factor 
      receptor (EGFR) and colony stimulating factor 1 receptor (CSF-1R) signaling.
PG  - 519-27
LID - 10.2119/molmed.2011.00217 [doi]
AB  - Glioblastoma multiforme is a deadly cancer for which current treatment options 
      are limited. The ability of glioblastoma tumor cells to infiltrate the 
      surrounding brain parenchyma critically limits the effectiveness of current 
      treatments. We investigated how microglia, the resident macrophages of the brain, 
      stimulate glioblastoma cell invasion. We first examined the ability of normal 
      microglia from C57Bl/6J mice to stimulate GL261 glioblastoma cell invasion in 
      vitro. We found that microglia stimulate the invasion of GL261 glioblastoma cells 
      by approximately eightfold in an in vitro invasion assay. Pharmacological 
      inhibition of epidermal growth factor receptor (EGFR) strongly inhibited 
      microglia-stimulated invasion. Furthermore, blockade of colony stimulating factor 
      1 receptor (CSF-1R) signaling using ribonucleic acid (RNA) interference or 
      pharmacological inhibitors completely inhibited microglial enhancement of 
      glioblastoma invasion. GL261 cells were found to constitutively secrete CSF-1, 
      the levels of which were unaffected by epidermal growth factor (EGF) stimulation, 
      EGFR inhibition or coculture with microglia. CSF-1 only stimulated microglia 
      invasion, whereas EGF only stimulated glioblastoma cell migration, demonstrating 
      a synergistic interaction between these two cell types. Finally, using PLX3397 (a 
      CSF-1R inhibitor that can cross the blood-brain barrier) in live animals, we 
      discovered that blockade of CSF-1R signaling in vivo reduced the number of 
      tumor-associated microglia and glioblastoma invasion. These data indicate that 
      glioblastoma and microglia interactions mediated by EGF and CSF-1 can enhance 
      glioblastoma invasion and demonstrate the possibility of inhibiting glioblastoma 
      invasion by targeting glioblastoma-associated microglia via inhibition of the 
      CSF-1R.
FAU - Coniglio, Salvatore J
AU  - Coniglio SJ
AD  - Department of Anatomy and Structural Biology, Albert Einstein College of 
      Medicine, Bronx, New York 10461, USA. salvatore.coniglio@einstein.yu.edu
FAU - Eugenin, Eliseo
AU  - Eugenin E
FAU - Dobrenis, Kostantin
AU  - Dobrenis K
FAU - Stanley, E Richard
AU  - Stanley ER
FAU - West, Brian L
AU  - West BL
FAU - Symons, Marc H
AU  - Symons MH
FAU - Segall, Jeffrey E
AU  - Segall JE
LA  - eng
GR  - P01 CA100324/CA/NCI NIH HHS/United States
GR  - R01 MH096625/MH/NIMH NIH HHS/United States
GR  - P30 CA13330/CA/NCI NIH HHS/United States
GR  - R01 CA25604/CA/NCI NIH HHS/United States
GR  - 11-0135/AICR_/Worldwide Cancer Research/United Kingdom
GR  - P01 CA 100324/CA/NCI NIH HHS/United States
GR  - P30 CA013330/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20120509
PL  - England
TA  - Mol Med
JT  - Molecular medicine (Cambridge, Mass.)
JID - 9501023
RN  - 62229-50-9 (Epidermal Growth Factor)
RN  - 81627-83-0 (Macrophage Colony-Stimulating Factor)
RN  - EC 2.7.10.1 (EGFR protein, mouse)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - EC 2.7.10.1 (Receptor, Macrophage Colony-Stimulating Factor)
SB  - IM
MH  - Animals
MH  - Brain Neoplasms/*metabolism/pathology
MH  - Cell Line, Tumor
MH  - Cell Proliferation
MH  - Cells, Cultured
MH  - Chemotaxis
MH  - Epidermal Growth Factor/metabolism
MH  - ErbB Receptors/*metabolism
MH  - Glioblastoma/*metabolism/pathology
MH  - Humans
MH  - Macrophage Colony-Stimulating Factor/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Microglia/*physiology
MH  - Neoplasm Invasiveness
MH  - Receptor, Macrophage Colony-Stimulating Factor/*antagonists & 
      inhibitors/metabolism
PMC - PMC3356419
EDAT- 2012/02/02 06:00
MHDA- 2012/09/05 06:00
PMCR- 2012/01/27
CRDT- 2012/02/02 06:00
PHST- 2011/06/23 00:00 [received]
PHST- 2012/01/26 00:00 [accepted]
PHST- 2012/02/02 06:00 [entrez]
PHST- 2012/02/02 06:00 [pubmed]
PHST- 2012/09/05 06:00 [medline]
PHST- 2012/01/27 00:00 [pmc-release]
AID - molmed.2011.00217 [pii]
AID - 11_00217_coniglio [pii]
AID - 10.2119/molmed.2011.00217 [doi]
PST - epublish
SO  - Mol Med. 2012 May 9;18(1):519-27. doi: 10.2119/molmed.2011.00217.