BMP signaling mediates glioma stem cell quiescence and confers treatment resistance in glioblastoma

Rohit Sachdeva, Megan Wu, Kevin Johnson, Hyunsoo Kim, Angela Celebre, Uswa Shahzad, Maya Srikanth Graham, John A. Kessler, Jeffrey H. Chuang, Jason Karamchandani, Markus Bredel, Roel Verhaak, Sunit Das*

*Corresponding author for this work

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4 Scopus citations

Abstract

Despite advances in therapy, glioblastoma remains an incurable disease with a dismal prognosis. Recent studies have implicated cancer stem cells within glioblastoma (glioma stem cells, GSCs) as mediators of therapeutic resistance and tumor progression. In this study, we investigated the role of the transforming growth factor-β (TGF-β) superfamily, which has been found to play an integral role in the maintenance of stem cell homeostasis within multiple stem cell systems, as a mediator of stem-like cells in glioblastoma. We find that BMP and TGF-β signaling define divergent molecular and functional identities in glioblastoma, and mark relatively quiescent and proliferative GSCs, respectively. Treatment of GSCs with BMP inhibits cell proliferation, but does not abrogate their stem-ness, as measured by self-renewal and tumorigencity. Further, BMP pathway activation confers relative resistance to radiation and temozolomide chemotherapy. Our findings define a quiescent cancer stem cell population in glioblastoma that may be a cellular reservoir for tumor recurrence following cytotoxic therapy.

Original languageEnglish (US)
Article number14569
JournalScientific reports
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2019

ASJC Scopus subject areas

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    Sachdeva, R., Wu, M., Johnson, K., Kim, H., Celebre, A., Shahzad, U., Graham, M. S., Kessler, J. A., Chuang, J. H., Karamchandani, J., Bredel, M., Verhaak, R., & Das, S. (2019). BMP signaling mediates glioma stem cell quiescence and confers treatment resistance in glioblastoma. Scientific reports, 9(1), [14569]. https://doi.org/10.1038/s41598-019-51270-1