Aberrant mesenchymal differentiation of glioma stem-like cells: Implications for therapeutic targeting

Veerakumar Balasubramaniyan, Brian Vaillant, Shuzhen Wang, Joy Gumin, M. Elena Butalid, Ke Sai, Farah Mukheef, Se Hoon Kim, H. W.G.M. Boddeke, Frederick Lang, Kenneth Aldape, Erik P. Sulman, Krishna P. Bhat, Howard Colman

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15 Citations (Scopus)

Abstract

Differentiation has been proposed as a therapeutic strategy for glioblastoma (GBM) in part due to observations of stem-like cells in GBM that have been shown to undergo terminal differentiation in response to growth factor withdrawal and BMP activation. However, the effects of long term exposure to serum culture conditions on glioma sphere cultures/glioma stem-like cells (GSCs) have not been examined. Here we show that GSCs retained both neurosphere formation and tumor initiation abilities after short or long term serum exposure. Under these conditions, GSCs expressed both neural lineage and stem cell markers, highlighting the aberrant pseudo-differentiation state. GSCs maintained under adherent serum cultured conditions continued to proliferate and initiate tumor formation with efficiencies similar to GSCs maintained under proliferating (neurosphere) conditions. Proneural (PN) GSCs under serum exposure showed an induction of mesenchymal (MES) gene expression signatures. Our data indicate that exposure to serum containing media result in aberrant differentiation (e.g. toward MES lineage) and activation of alternative oncogenic pathways in GSCs.

Original languageEnglish
Pages (from-to)31007-31017
Number of pages11
JournalOncotarget
Volume6
Issue number31
DOIs
Publication statusPublished - 2015

All Science Journal Classification (ASJC) codes

  • Oncology

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    Balasubramaniyan, V., Vaillant, B., Wang, S., Gumin, J., Elena Butalid, M., Sai, K., Mukheef, F., Kim, S. H., Boddeke, H. W. G. M., Lang, F., Aldape, K., Sulman, E. P., Bhat, K. P., & Colman, H. (2015). Aberrant mesenchymal differentiation of glioma stem-like cells: Implications for therapeutic targeting. Oncotarget, 6(31), 31007-31017. https://doi.org/10.18632/oncotarget.5219