Hyperdiploid tumor cells increase phenotypic heterogeneity within Glioblastoma tumors

Donovan, Prudence, Cato, Kathleen, Legaie, Roxane, Jayalath, Rumal, Olsson, Gemma, Hall, Bruce, Olson, Sarah, Boros, Samuel, Reynolds, Brent A. and Harding, Angus (2014) Hyperdiploid tumor cells increase phenotypic heterogeneity within Glioblastoma tumors. Molecular Biosystems, 10 4: 741-758. doi:10.1039/c3mb70484j


Author Donovan, Prudence
Cato, Kathleen
Legaie, Roxane
Jayalath, Rumal
Olsson, Gemma
Hall, Bruce
Olson, Sarah
Boros, Samuel
Reynolds, Brent A.
Harding, Angus
Title Hyperdiploid tumor cells increase phenotypic heterogeneity within Glioblastoma tumors
Journal name Molecular Biosystems   Check publisher's open access policy
ISSN 1742-206X
1742-2051
Publication date 2014-01-01
Year available 1987
Sub-type Article (original research)
DOI 10.1039/c3mb70484j
Open Access Status Not Open Access
Volume 10
Issue 4
Start page 741
End page 758
Total pages 18
Place of publication Cambridge, United Kingdom
Publisher Royal Society of Chemistry
Language eng
Abstract Here we report the identification of a proliferative, viable, and hyperdiploid tumor cell subpopulation present within Glioblastoma (GB) patient tumors. Using xenograft tumor models, we demonstrate that hyperdiploid cell populations are maintained in xenograft tumors and that clonally expanded hyperdiploid cells support tumor formation and progression in vivo. In some patient tumorsphere lines, hyperdiploidy is maintained during long-term culture and in vivo within xenograft tumor models, suggesting that hyperdiploidy can be a stable cell state. In other patient lines hyperdiploid cells display genetic drift in vitro and in vivo, suggesting that in these patients hyperdiploidy is a transient cell state that generates novel phenotypes, potentially facilitating rapid tumor evolution. We show that the hyperdiploid cells are resistant to conventional therapy, in part due to infrequent cell division due to a delay in the G0/G1 phase of the cell cycle. Hyperdiploid tumor cells are significantly larger and more metabolically active than euploid cancer cells, and this correlates to an increased sensitivity to the effects of glycolysis inhibition. Together these data identify GB hyperdiploid tumor cells as a potentially important subpopulation of cells that are well positioned to contribute to tumor evolution and disease recurrence in adult brain cancer patients, and suggest tumor metabolism as a promising point of therapeutic intervention against this subpopulation.
Keyword Hematopoietic Stem-Cells
Growth-Factor Receptor
Breast-Cancer Cells
Human Glioma-Cells
Chronic Myeloid-Leukemia
Human-Malignant Gliomas
Central-Nervous-System
Tyrosine Kinase Genes
Astrocytic Tumors
Initiating Cells
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
Institute for Molecular Bioscience - Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 3 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 3 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Sun, 06 Apr 2014, 10:04:26 EST by System User on behalf of Institute for Molecular Bioscience