PMID- 23788430
OWN - NLM
STAT- MEDLINE
DCOM- 20140615
LR  - 20211021
IS  - 1477-9137 (Electronic)
IS  - 0021-9533 (Print)
IS  - 0021-9533 (Linking)
VI  - 126
IP  - Pt 16
DP  - 2013 Aug 15
TI  - Non-invasive neural stem cells become invasive in vitro by combined FGF2 and BMP4 
      signaling.
PG  - 3533-40
LID - 10.1242/jcs.125757 [doi]
AB  - Neural stem cells (NSCs) typically show efficient self-renewal and selective 
      differentiation. Their invasion potential, however, is not well studied. In this 
      study, Sox2-positive NSCs from the E14.5 rat cortex were found to be non-invasive 
      and showed only limited migration in vitro. By contrast, FGF2-expanded NSCs 
      showed a strong migratory and invasive phenotype in response to the combination 
      of FGF2 and BMP4. Invasive NSCs expressed Podoplanin (PDPN) and p75NGFR (Ngfr) at 
      the plasma membrane after exposure to FGF2 and BMP4. FGF2 and BMP4 together 
      upregulated the expression of Msx1, Snail1, Snail2, Ngfr, which are all found in 
      neural crest (NC) cells during or after epithelial-mesenchymal transition (EMT), 
      but not in forebrain stem cells. Invasive cells downregulated the expression of 
      Olig2, Sox10, Egfr, Pdgfra, Gsh1/Gsx1 and Gsh2/Gsx2. Migrating and invasive NSCs 
      had elevated expression of mRNA encoding Pax6, Tenascin C (TNC), PDPN, Hey1, 
      SPARC, p75NGFR and Gli3. On the basis of the strongest upregulation in 
      invasion-induced NSCs, we defined a group of five key invasion-related genes: 
      Ngfr, Sparc, Snail1, Pdpn and Tnc. These genes were co-expressed and upregulated 
      in seven samples of glioblastoma multiforme (GBM) compared with normal human 
      brain controls. Induction of invasion and migration led to low expression of 
      differentiation markers and repressed proliferation in NSCs. Our results indicate 
      that normal forebrain stem cells have the inherent ability to adopt a glioma-like 
      invasiveness. The results provide a novel in vitro system to study stem cell 
      invasion and a novel glioma invasion model: tumoral abuse of the developmental 
      dorsoventral identity regulation.
FAU - Sailer, Martin H M
AU  - Sailer MH
AD  - Department of Biomedicine, Brain Tumor Biology Laboratory, Klingelbergstrasse 
      50/70, CH-4056 Basel, Switzerland. martin.sailer@usb.ch
FAU - Gerber, Alexandra
AU  - Gerber A
FAU - Tostado, Cristobal
AU  - Tostado C
FAU - Hutter, Gregor
AU  - Hutter G
FAU - Cordier, Dominik
AU  - Cordier D
FAU - Mariani, Luigi
AU  - Mariani L
FAU - Ritz, Marie-Francoise
AU  - Ritz MF
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130620
PL  - England
TA  - J Cell Sci
JT  - Journal of cell science
JID - 0052457
RN  - 0 (Bone Morphogenetic Protein 4)
RN  - 103107-01-3 (Fibroblast Growth Factor 2)
SB  - IM
MH  - Animals
MH  - Bone Morphogenetic Protein 4/genetics/*metabolism
MH  - Cell Movement/physiology
MH  - Female
MH  - Fibroblast Growth Factor 2/genetics/*metabolism
MH  - Humans
MH  - Immunohistochemistry
MH  - Neural Stem Cells/*cytology/*metabolism
MH  - Pregnancy
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Signal Transduction
PMC - PMC3744023
OTO - NOTNLM
OT  - BMP4
OT  - FGF2
OT  - Invasion
OT  - Migration
OT  - Neural stem cell
EDAT- 2013/06/22 06:00
MHDA- 2014/06/16 06:00
PMCR- 2014/08/15
CRDT- 2013/06/22 06:00
PHST- 2013/06/22 06:00 [entrez]
PHST- 2013/06/22 06:00 [pubmed]
PHST- 2014/06/16 06:00 [medline]
PHST- 2014/08/15 00:00 [pmc-release]
AID - jcs.125757 [pii]
AID - 10.1242/jcs.125757 [doi]
PST - ppublish
SO  - J Cell Sci. 2013 Aug 15;126(Pt 16):3533-40. doi: 10.1242/jcs.125757. Epub 2013 
      Jun 20.