gms | German Medical Science

63. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC)
Joint Meeting mit der Japanischen Gesellschaft für Neurochirurgie (JNS)

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

13. - 16. Juni 2012, Leipzig

Identification of specific proteins for glioma-initiating cells

Meeting Abstract

  • B. Schatlo - Department of Neurosurgery, University of Geneva,Geneva, Switzerland
  • M. Tenan - Department of Clinical Neurosciences, Geneva University Hospitals, Switzerland
  • D. Marino - Department of Clinical Neurosciences, Geneva University Hospitals, Switzerland
  • K. Schaller - Department of Neurosurgery, University of Geneva,Geneva, Switzerland
  • I. Radovanovic - Department of Neurosurgery, University of Geneva,Geneva, Switzerland
  • V.C. Clément-Schatlo - Department of Clinical Neurosciences, Geneva University Hospitals, Switzerland

Deutsche Gesellschaft für Neurochirurgie. Japanische Gesellschaft für Neurochirurgie. 63. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit der Japanischen Gesellschaft für Neurochirurgie (JNS). Leipzig, 13.-16.06.2012. Düsseldorf: German Medical Science GMS Publishing House; 2012. DocFR.07.08

DOI: 10.3205/12dgnc221, URN: urn:nbn:de:0183-12dgnc2214

Veröffentlicht: 4. Juni 2012

© 2012 Schatlo et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielfältigt, verbreitet und öffentlich zugänglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

Objective: Malignant gliomas remain one of the most aggressive diseases with a 2-year survival rate of 32% with today's available standard treatments. A number of biomarkers such as GFAP, YKL-40 and S100b can be found in the blood of a proportion of glioma patients. However, it is unknown whether the cells which express and secrete these markers are glioma-initiating cells (GIC) or cells from the bulk representing the differentiated part of the tumor. A specific biomarker for GIC is not available, but could enhance our ability to characterize the biological behavior of a tumor.

Methods: In order to evaluate the specificity of the above mentioned protein markers for glioma-initiating cells, we employed a recently published procedure to discriminate glioma-initiating cells from the non-initiating cells within brain tumors (Clément et al, Nature Methods 2010). Identification of novel markers was performed using screening and validation of GIC vs. non-GIC in human glioblastoma populations.

Results: Biomarkers such as GFAP or YKL-40 showed low or almost no selective expression in the GIC compartment. S100b was predominantly expressed by GIC, but at equal levels by non-tumorigenic brain cells. We therefore screened for novel and specific biomarkers in purified initiating and non-initiating cell populations. Using Illumina microarrays, we identified 411 candidate genes (criteria: 2 fold change and p < 0.05) and selected 11 candidate biomarker_genes for the GIC compartment and 10 candidate biomarker genes for the non-GIC compartment. Using quantitative real-time PCR and immunochemistry/flow cytometry, we validated 2 biomarkers for GICs (SDx203 and SDx206) and 2 for non-GICs at the mRNA and at the protein level.

Conclusions: Despite their clinical relevance for the tumor bulk as a whole, currently known biomarkers cannot be used as specific biomarkers for glioma-initiating cells. We identified specific biomarkers for glioma-initiating cells based on a cell-sorting approach validated by gene expression and protein analysis. Further research will focus on the molecular biology of the subpopulation of GICs within the tumor and assess the clinical value of the biomarkers SDx203 and SDx206 to identify GIC, e.g. intraoperatively.