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  • Rebetz, JohanLund University,Lunds universitet,Neurokirurgi,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Neurosurgery,Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine (author)

Glial Progenitor-Like Phenotype in Low-Grade Glioma and Enhanced CD133-Expression and Neuronal Lineage Differentiation Potential in High-Grade Glioma

  • Article/chapterEnglish2008

Publisher, publication year, extent ...

  • 2008-04-09
  • Public Library of Science (PLoS),2008
  • electronicrdacarrier

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  • LIBRIS-ID:oai:lup.lub.lu.se:cc2fd871-b9a0-48b4-9af5-611da81653e7
  • https://lup.lub.lu.se/record/1531260URI
  • https://doi.org/10.1371/journal.pone.0001936DOI
  • https://lup.lub.lu.se/record/1147585URI

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  • Language:English
  • Summary in:English

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  • Subject category:art swepub-publicationtype
  • Subject category:ref swepub-contenttype

Notes

  • Background: While neurosphere-as well as xenograft tumor-initiating cells have been identified in gliomas, the resemblance between glioma cells and neural stem/progenitor cells as well as the prognostic value of stem/progenitor cell marker expression in glioma are poorly clarified. Methodology/Principal Findings: Viable glioma cells were characterized for surface marker expression along the glial genesis hierarchy. Six low-grade and 17 high-grade glioma specimens were flow-cytometrically analyzed for markers characteristics of stem cells (CD133); glial progenitors (PDGFR alpha, A2B5, O4, and CD44); and late oligodendrocyte progenitors (O1). In parallel, the expression of glial fibrillary acidic protein (GFAP), synaptophysin and neuron-specific enolase (NSE) was immunohistochemically analyzed in fixed tissue specimens. Irrespective of the grade and morphological diagnosis of gliomas, glioma cells concomitantly expressed PDGFRa, A2B5, O4, CD44 and GFAP. In contrast, O1 was weakly expressed in all low-grade and the majority of high-grade glioma specimens analyzed. Co-expression of neuronal markers was observed in all high-grade, but not low-grade, glioma specimens analyzed. The rare CD133 expressing cells in low-grade glioma specimens typically co-expressed vessel endothelial marker CD31. In contrast, distinct CD133 expression profiles in up to 90% of CD45-negative glioma cells were observed in 12 of the 17 high-grade glioma specimens and the majority of these CD133 expressing cells were CD31 negative. The CD133 expression correlates inversely with length of patient survival. Surprisingly, cytogenetic analysis showed that gliomas contained normal and abnormal cell karyotypes with hitherto indistinguishable phenotype. Conclusions/Significance: This study constitutes an important step towards clarification of lineage commitment and differentiation blockage of glioma cells. Our data suggest that glioma cells may resemble expansion of glial lineage progenitor cells with compromised differentiation capacity downstream of A2B5 and O4 expression. The concurrent expression of neuronal markers demonstrates that high-grade glioma cells are endowed with multi-lineage differentiation potential in vivo. Importantly, enhanced CD133 expression marks a poor prognosis in gliomas.

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  • Tian, DongpingLund University,Lunds universitet,Neurokirurgi,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Neurosurgery,Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)med-dnt (author)
  • Persson, AnnetteLund University,Lunds universitet,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Department of Clinical Sciences, Lund,Faculty of Medicine,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund(Swepub:lu)pat-ape (author)
  • Widegren, BengtLund University,Lunds universitet,Neurokirurgi,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Biologiska institutionen,Naturvetenskapliga fakulteten,Neurosurgery,Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine,Department of Biology,Faculty of Science(Swepub:lu)wbl-bwi (author)
  • Salford, LeifLund University,Lunds universitet,Neurokirurgi,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Neurosurgery,Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)nkir-lsa (author)
  • Englund, ElisabetLund University,Lunds universitet,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Department of Clinical Sciences, Lund,Faculty of Medicine,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund(Swepub:lu)pat-een (author)
  • Gisselsson Nord, DavidLund University,Lunds universitet,Avdelningen för klinisk genetik,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Clinical Genetics,Department of Laboratory Medicine,Faculty of Medicine(Swepub:lu)kgen-dgi (author)
  • Fan, XiaolongLund University,Lunds universitet,Neurokirurgi,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Neurosurgery,Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)molm-xfa (author)
  • NeurokirurgiSektion IV (creator_code:org_t)

Related titles

  • In:PLoS ONE: Public Library of Science (PLoS)10:6, s. 1107-11071932-6203
  • In:Neuro-Oncology: Public Library of Science (PLoS)10:6, s. 1107-11071523-5866

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Rebetz, Johan
Tian, Dongping
Persson, Annette
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Neuro-Oncology
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