uu.seUppsala University Publications
Change search
ReferencesLink to record
Permanent link

Direct link
Identification of a SOX2-dependent subset of tumor- and sphere-forming glioblastoma cells with a distinct tyrosine kinase inhibitor sensitivity profile
Show others and affiliations
2011 (English)In: Neuro-Oncology, ISSN 1522-8517, E-ISSN 1523-5866, Vol. 13, no 11, 1178-1191 p.Article in journal (Refereed) Published
Abstract [en]

Putative cancer stem cells have been identified in glioblastomas and are associated with radio- and chemoresistance. Further knowledge about these cells is thus highly warranted for the development of better glioblastoma therapies. Gene expression analyses of 11 high-grade glioma cultures identified 2 subsets, designated type A and type B cultures. The type A cultures displayed high expression of CXCR4, SOX2, EAAT1, and GFAP and low expression of CNP, PDGFRB, CXCL12, and extracellular matrix proteins. Clinical significance of the 2 types was indicated by the expression of type A-and type B-defining genes in different clinical glioblastoma samples. Classification of glioblastomas with type A- and type B-defining genes generated 2 groups of tumors composed predominantly of the classical, neural, and/or proneural subsets and the mesenchymal subset, respectively. Furthermore, tumors with EGFR mutations were enriched in the group of type A samples. Type A cultures possessed a higher capacity to form xenograft tumors and neurospheres and displayed low or no sensitivity to monotreatment with PDGF-and IGF-1-receptor inhibitors but were efficiently growth inhibited by combination treatment with low doses of these 2 inhibitors. Furthermore, siRNA-induced downregulation of SOX2 reduced sphere formation of type A cultures, decreased expression of type A-defining genes, and conferred sensitivity to monotreatment with PDGF-and IGF-1receptor inhibitors. The present study thus describes a tumor-and neurosphere-forming SOX2-dependent subset of glioblastoma cultures characterized by a gene expression signature similar to that of the recently described classical, proneural, and/or neural subsets of glioblastoma. The findings that resistance to PDGF-and IGF-1-receptor inhibitors is related to SOX2 expression and can be overcome by combination treatment should be considered in ongoing efforts to develop novel stem cell-targeting therapies.

Place, publisher, year, edition, pages
2011. Vol. 13, no 11, 1178-1191 p.
Keyword [en]
cancer stem cell, glioma, SOX2, subset
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-163680DOI: 10.1093/neuonc/nor113ISI: 000297025500003OAI: oai:DiVA.org:uu-163680DiVA: diva2:464866
Available from: 2011-12-14 Created: 2011-12-13 Last updated: 2011-12-14Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full text

Search in DiVA

By author/editor
Hesselager, Göran
By organisation
In the same journal
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 182 hits
ReferencesLink to record
Permanent link

Direct link