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

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Oligodendrocyte progenitor cells can act as cell of origin for experimental glioma
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology. (Lene Uhrbom)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
Show others and affiliations
2009 (English)In: Oncogene, ISSN 0950-9232, E-ISSN 1476-5594, Vol. 28, no 23, 2266-2275 p.Article in journal (Refereed) Published
Abstract [en]

Gliomas are primary brain tumors mainly affecting adults. The cellular origin is unknown. The recent identification of tumor-initiating cells in glioma, which share many similarities with normal neural stem cells, has suggested the cell of origin to be a transformed neural stem cell. In previous studies, using the RCAS/tv-a mouse model, platelet-derived growth factor B (PDGF-B)-induced gliomas have been generated from nestin or glial fibrillary acidic protein-expressing cells, markers of neural stem cells. To investigate if committed glial progenitor cells could be the cell of origin for glioma, we generated the Ctv-a mouse where tumor induction would be restricted to myelinating oligodendrocyte progenitor cells (OPCs) expressing 2',3'-cyclic nucleotide 3'-phosphodiesterase. We showed that PDGF-B transfer to OPCs could induce gliomas with an incidence of 33%. The majority of tumors resembled human WHO grade II oligodendroglioma based on close similarities in histopathology and expression of cellular markers. Thus, with the Ctv-a mouse we have showed that the cell of origin for glioma may be a committed glial progenitor cell.

Place, publisher, year, edition, pages
2009. Vol. 28, no 23, 2266-2275 p.
Keyword [en]
glioma, cell of origin, neural stem cell, oligodendrocyte progenitor cell, glial cell, PDGF
National Category
Medical and Health Sciences
Research subject
Molecular Medicine
Identifiers
URN: urn:nbn:se:uu:diva-109379DOI: 10.1038/onc.2009.76ISI: 000266886300003PubMedID: 19421151OAI: oai:DiVA.org:uu-109379DiVA: diva2:272190
Available from: 2009-10-14 Created: 2009-10-14 Last updated: 2017-12-12Bibliographically approved
In thesis
1. Cellular Origin and Development of Glioma
Open this publication in new window or tab >>Cellular Origin and Development of Glioma
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Gliomas are the most common primary tumors of the central nervous system believed to arise from glial cells. Invasive growth and inherent propensity for malignant progression make gliomas incurable despite extensive treatment. I have developed a life-like orthotopic glioma model and used this and other in vivo models to study basic mechanisms of glioma development and treatment.

Previous studies had indicated that experimental gliomas could arise from glial stem cells and astrocytes. The present thesis describes the making and characterization of a novel mouse model, Ctv-a, where gliomas are induced from oligodendrocyte progenitor cells (OPCs). Our study shows that OPCs have the capacity to give rise to gliomas and suggests in light of previous data that the differentiation state of the cell of origin affects tumor malignancy.

CDKN2A encodes p16INK4a and p14ARF (p19Arf in mouse) commonly inactivated in malignant glioma. Their roles in experimental glioma have been extensively studied and both proteins have tumor suppressor functions in glial stem cells and astrocytes. Here, we demonstrate that p19Arf only could suppress gliomagenesis in OPCs while p16Ink4a had no tumor suppressive effect.

Functional DNA repair is pivotal for maintaining genome integrity, eliminating unsalvageable cells and inhibiting tumorigenesis. We have studied how RAD51, a central protein of homology-directed repair, affected experimental glioma development and have found that expression of RAD51 may protect against genomic instability and tumor development.

Angiogenesis, the formation of new blood vessels from pre-existing ones, is a central feature of malignant progression in glioma. Antiangiogenic treatment by inhibition of vascular endothelial growth factor receptor signaling is used in the clinic for treatment of some cancers. We have investigated the effect of an alternative antiangiogenic protein, histidine-rich glycoprotein (HRG), on glioma development and found that HRG could inhibit the formation of malignant gliomas and completely prevent the formation of glioblastoma.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2009. 59 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 491
Keyword
Glioma, brain tumor, PDGF, RCAS/TV-A, cell of origin, glial cell, oligodendrocyte progenitor cell, DNA repair, homology-directed repair, RAD51, angiogenesis, histidine-rich glycoprotein
National Category
Cell and Molecular Biology
Research subject
Molecular Medicine
Identifiers
urn:nbn:se:uu:diva-109486 (URN)978-91-554-7640-3 (ISBN)
Public defence
2009-12-04, Rudbecksalen, Rudbecklaboratoriet, Dag Hammarskjölds väg 20, Uppsala, 09:15 (English)
Opponent
Supervisors
Available from: 2009-11-13 Created: 2009-10-15 Last updated: 2009-11-13Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMedArbetets abstract på tidsskriftens hemsida

Authority records BETA

Kastemar, MarianneSmits, AnjaUhrbom, Lene

Search in DiVA

By author/editor
Kastemar, MarianneSmits, AnjaUhrbom, Lene
By organisation
Department of Genetics and PathologyDepartment of Neuroscience
In the same journal
Oncogene
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 1081 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf