Artikel
Aberrant self-renewal and quiescence contribute to glioblastoma aggressiveness
Suche in Medline nach
Autoren
-
Benito Campos
- Sektion Experimentelle Neurochirurgie, Neurochirurgische Klinik, Universitätsklinikum Heidelberg, Heidelberg
-
Tilman Schneider
- Sektion Experimentelle Neurochirurgie, Neurochirurgische Klinik, Universitätsklinikum Heidelberg, Heidelberg
-
Christopher Sliwinski
- Sektion Experimentelle Neurochirurgie, Neurochirurgische Klinik, Universitätsklinikum Heidelberg, Heidelberg
-
Aline Baader
- Sektion Experimentelle Neurochirurgie, Neurochirurgische Klinik, Universitätsklinikum Heidelberg, Heidelberg
-
Christel Herold-Mende
- Sektion Experimentelle Neurochirurgie, Neurochirurgische Klinik, Universitätsklinikum Heidelberg, Heidelberg
-
Andreas Unterberg
- Sektion Experimentelle Neurochirurgie, Neurochirurgische Klinik, Universitätsklinikum Heidelberg, Heidelberg
| Veröffentlicht: | 21. Mai 2013 |
|---|
Gliederung
Text
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 of devising new isolation methods based on common functional and phenotypic criteria.
Method: In this study we made use of a collagen-based self-renewal assay, to screen for clonogenic cell subpopulation in malignant gliomas. Cells were profiled using a gene expression chip and tested for tumor formation capacity in an orthotopic mouse model. Label retention was used to detect quiescent tumor cells.
Results: In a panel of glioblastoma cell lines (n=21) we identified several cell lines enriched for cells with enhanced self-renewal capacity. These cell lines were capable of matrix-independent growth and formed fast-growing, orthotopic tumors in mice. Employing isolation and re-plating techniques, we could further show that these cells invariably re-established a cellular hierarchy through a series of asymmetric cell divisions. However, the ratio of symmetric to asymmetric cell divisions seemed to be pathologically increased and was linked to idiosyncratic transcriptomal changes as well as to poor overall survival of corresponding patients. Finally, through label-retention experiments we further identified a subpopulation of quiescent and chemo-resistant cells, which retained the ability to reinitiate growth of secondary cell clones and thus, might play a role in tumor recurrence after therapy.
Conclusions: Altogether, our results suggest tumor quiescence and aberrant proliferations influence the aggressiveness of glioblastoma.
