Journal Article

DKFZ-2018-00223

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Quiescent sox2(+) cells drive hierarchical growth and relapse in sonic hedgehog subgroup medulloblastoma.

Vanner, R. J. ; Remke, M. ; Gallo, M. ; Selvadurai, H. J. ; Coutinho, F. ; Lee, L. ; Kushida, M. ; Head, R. ; Morrissy, S. ; Zhu, X. ; Aviv, T. ; Voisin, V. ; Clarke, I. D. ; Li, Y. ; Mungall, A. J. ; Moore, R. A. ; Ma, Y. ; Jones, S. J. M. ; Marra, M. A. ; Malkin, D. ; Northcott, P. A. ; Kool, M.DKFZ* ; Pfister, S.DKFZ* ; Bader, G. ; Hochedlinger, K. ; Korshunov, A.DKFZ* ; Taylor, M. D. ; Dirks, P. B.

2014
Cell Press Cambridge, Mass.

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Please use a persistent id in citations: doi:10.1016/j.ccr.2014.05.005

Abstract: Functional heterogeneity within tumors presents a significant therapeutic challenge. Here we show that quiescent, therapy-resistant Sox2(+) cells propagate sonic hedgehog subgroup medulloblastoma by a mechanism that mirrors a neurogenic program. Rare Sox2(+) cells produce rapidly cycling doublecortin(+) progenitors that, together with their postmitotic progeny expressing NeuN, comprise tumor bulk. Sox2(+) cells are enriched following anti-mitotic chemotherapy and Smoothened inhibition, creating a reservoir for tumor regrowth. Lineage traces from Sox2(+) cells increase following treatment, suggesting that this population is responsible for relapse. Targeting Sox2(+) cells with the antineoplastic mithramycin abrogated tumor growth. Addressing functional heterogeneity and eliminating Sox2(+) cells presents a promising therapeutic paradigm for treatment of sonic hedgehog subgroup medulloblastoma.

Keyword(s): Antigens, Nuclear ; Antineoplastic Agents ; Biomarkers, Tumor ; Hedgehog Proteins ; Microtubule-Associated Proteins ; Nerve Tissue Proteins ; NeuN protein, mouse ; Neuropeptides ; Nuclear Proteins ; Patched Receptors ; Receptors, Cell Surface ; Receptors, G-Protein-Coupled ; SHH protein, human ; SMO protein, human ; SOX2 protein, human ; SOXB1 Transcription Factors ; Shh protein, mouse ; Smo protein, mouse ; Smoothened Receptor ; Sox2 protein, mouse ; doublecortin protein ; neuronal nuclear antigen NeuN, human ; Plicamycin

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Contributing Institute(s):

1. Pädiatrische Neuroonkologie (B062)
2. KKE Neuropathologie (G380)

Research Program(s):

1. 312 - Functional and structural genomics (POF3-312) (POF3-312)

Appears in the scientific report 2014

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Database coverage:
; BIOSIS Previews ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; Ebsco Academic Search ; IF >= 20 ; JCR ; NCBI Molecular Biology Database ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Thomson Reuters Master Journal List ; Web of Science Core Collection

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