A paired comparison between glioblastoma "stem cells" and differentiated cells. Issue 7 (17th November 2015)

• Record Type: Journal Article
• Authors: Schneider, Matthias; Ströbele, Stephanie; Nonnenmacher, Lisa; Siegelin, Markus D.; Tepper, Melanie; Stroh, Sebastien; Hasslacher, Sebastian; Enzenmüller, Stefanie; Strauss, Gudrun; Baumann, Bernd; Karpel‐Massler, Georg; Westhoff, Mike‐Andrew; Debatin, Klaus‐Michael; Halatsch, Marc‐Eric
• Is Part Of: International journal of cancer. Volume 138:Issue 7(2016:Apr. 01)
• Page Start: 1709
• Page End: 1718
• Publication Date: 2015-11-17
• Subjects: glioblastoma -- brain tumour -- cancer stem cell; Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.29908
• Languages: English
• ISSNs: 0020-7136

Abstract

Abstract : Cancer stem cells (CSC) have been postulated to be responsible for the key features of a malignancy and its maintenances, as well as therapy resistance, while differentiated cells are believed to make up the rapidly growing tumour bulk. It is therefore important to understand the characteristics of those two distinct cell populations in order to devise treatment strategies which effectively target both cohorts, in particular with respect to cancers, such as glioblastoma. Glioblastoma is the most common primary brain tumour in adults, with a mean patient survival of 12–15 months. Importantly, therapeutic improvements have not been forthcoming in the last decade. In this study we compare key features of three pairs of glioblastoma cell populations, each pair consisting of stem cell‐like and differentiated cells derived from an individual patient. Our data suggest that while growth rates and expression of key survival‐ and apoptosis‐mediating proteins are more similar according to differentiation status than genetic similarity, we found no intrinsic differences in response to standard therapeutic interventions, namely exposure to radiation or the alkylating agent temozolomide. Interestingly, we could demonstrate that both stem cell‐like and differentiated cells possess the ability to form stem cell‐containing tumours in immunocompromised mice and that differentiated cells could potentially be dedifferentiated to potential stem cells. Taken together our data suggest that the differences between tumour stem cell and differentiated cell are particular fluent in glioblastoma. Abstract : What's new? The heterogeneity of different malignant cell populations within a tumor is a major mechanism of therapeutic resistance in cancer, and in glioblastoma such resistance is a leading obstacle to long‐term survival. This study shows that glioblastoma cell behaviour is more strongly dependent on differentiation status than on genetic identity. Moreover, glioblastoma was found to belong to the group of tumors that readily allow dedifferentiation. The findings significantly impact the direction of future therapeutic strategies for glioblastoma and provide context for recent data on differences in therapeutic resistance between different glioblastoma cell populations.