Artikel
Aberrant symmetric proliferation of stem-like tumor cells influences tumor malignancy in glioblastoma
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Veröffentlicht: | 28. April 2011 |
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Gliederung
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Objective: Stem-like tumor cells endowed with enhanced self-renewal capacity are believed to drive tumor growth in malignant gliomas. So far a variety of surrogate markers has been proposed to characterize and enrich these cells, emphasizing the need for devising new isolation methods based on common functional and phenotypic criteria.
Methods: In this study we made use of the neural colony-forming cell assay (NCFCA), a recently published self-renewal assay, to screen for clonogenic cell subpopulations in malignant gliomas.
Results: In a large panel of glioblastoma cell lines (n=24) we identified a series of cell lines enriched for cells with enhanced self-renewal capacity. Employing isolation and re-plating techniques, we were able to identify individual cells with the unique ability to reinitiate growth of secondary cell clones. Through label-retention experiments we could further show that these cells invariably re-established a cellular hierarchy in terms of self-renewal capacity through a series of asymmetric cell divisions. However, the ratio of symmetric to asymmetric cell "fate" divisions seemed to be pathologically increased. Finally, we were able to establish a link between the increased self-renewal in these cell lines in vitro and a poor overall survival among the corresponding patients.
Conclusions: Altogether, the NCFCA was found to be a valuable, marker-independent assay to study cells with aberrant self-renewal capacity in glioblastoma.