Cancer stem cells in glioblastoma—molecular signaling and therapeutic targeting

Abstract

Glioblastomas (GBMs) are highly lethal primary brain tumors. Despite current therapeutic advances in other solid cancers, the treatment of these malignant gliomas remains essentially palliative. GBMs are extremely resistant to conventional radiation and chemotherapies. We and others have demonstrated that a highly tumorigenic subpopulation of cancer cells called GBM stem cells (GSCs) promotes therapeutic resistance. We also found that GSCs stimulate tumor angiogenesis by expressing elevated levels of VEGF and contribute to tumor growth, which has been translated into a useful therapeutic strategy in the treatment of recurrent or progressive GBMs. Furthermore, stem cell-like cancer cells (cancer stem cells) have been shown to promote metastasis. Although GBMs rarely metastasize beyond the central nervous system, these highly infiltrative cancers often invade into normal brain tissues preventing surgical resection, and GSCs display an aggressive invasive phenotype. These studies suggest that targeting GSCs may effectively reduce tumor recurrence and significantly improve GBM treatment. Recent studies indicate that cancer stem cells share core signaling pathways with normal somatic or embryonic stem cells, but also display critical distinctions that provide important clues into useful therapeutic targets. In this review, we summarize the current understanding and advances in glioma stem cell research, and discuss potential targeting strategies for future development of anti-GSC therapies.

Comparison of Spheroids Formed by Rat Glioma Stem Cells and Neural Stem Cells Reveals Differences in Glucose Metabolism and Promising Therapeutic Applications

“…1, C and D) often overexpressed in human CSCs (28). In addition, injection of P7 neurospheres drastically increased the cancer cells tumorigenicity compared with that of adherent cells (Fig.…”

“…LDA and experimental estimation of the stem-like cell number in the population (28) showed that DCA gradually reduced the CSC ability to form spheroids, whereas that of NSCs were unaffected ( Fig. 3D and supplemental Fig.…”

Les multiples facettes d’un petit régulateur

“…Dans ce contexte, l'expression de miR-9/9* apparaît réguler, au sein de la masse tumorale, les propriétés de certaines cellules appelées cellules souches cancéreuses [34,35]. Ces cellules, qui ont un fort potentiel d'autorenouvellement à long terme, sont également plus résistantes à la chimiothérapie et sont ainsi considérées comme probablement responsables des rechutes [36]. Une étude montre que, dans les glioblastomes, ces cellules souches expriment un plus fort niveau de miR-9/9* [34].…”

Protein Kinase CK2 Content in GL261 Mouse Glioblastoma

“…A u t h o r ' s a c c e p t e d m a n u s c r i p t 3 The use of animal models in brain tumour research is mandatory in the search for new therapeutic targets due to obvious ethical restrictions related to human patients. The ideal animal model of GBM should reproduce the main characteristics of this neoplasm: characteristic growth pattern, infiltrative, but non-metastatic, tumour growth and poor immunogenicity (4).…”