In:
Journal of Cell Science, The Company of Biologists
Abstract:
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 non-invasive and showed only limited migration in vitro. In contrast, FGF2-expanded NSCs showed a strong migratory and invasive phenotype in response to the combination of both factors FGF2 and BMP4. Invasive NSCs expressed Podoplanin (PDPN) and p75NGFR at the plasma membrane after exposure to FGF2 and BMP4. The combination FGF2 and BMP4 upregulated the expression of Msx1, Snail1, Snail2, p75NGFR, genes that are 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, PDGFRalpha, Gsh1/Gsx1, and Gsh2/Gsx2. Migrating and invasive NSCs had elevated Pax6, Tenascin C (TNC), PDPN, Hey1, SPARC, p75NGFR and Gli3 mRNA expression. Based on strongest upregulation in invasion-induced NSCs, we defined a group of 5 key invasion-related genes: p75NGFR, SPARC, Snail1, PDPN and TNC. These genes were found co-expressed and upregulated in 7 samples of glioblastoma multiforme (GBM) compared to normal human brain controls. Induction of invasion/migration lead 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.
Type of Medium:
Online Resource
ISSN:
1477-9137
,
0021-9533
Language:
English
Publisher:
The Company of Biologists
Publication Date:
2013
detail.hit.zdb_id:
219171-4
detail.hit.zdb_id:
1483099-1
SSG:
12
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