| Literature DB >> 24954133 |
Robert J Vanner1, Marc Remke2, Marco Gallo3, Hayden J Selvadurai3, Fiona Coutinho1, Lilian Lee3, Michelle Kushida3, Renee Head3, Sorana Morrissy3, Xueming Zhu3, Tzvi Aviv3, Veronique Voisin4, Ian D Clarke5, Yisu Li6, Andrew J Mungall6, Richard A Moore6, Yussanne Ma6, Steven J M Jones6, Marco A Marra6, David Malkin7, Paul A Northcott8, Marcel Kool8, Stefan M Pfister9, Gary Bader4, Konrad Hochedlinger10, Andrey Korshunov11, Michael D Taylor2, Peter B Dirks12.
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.Entities:
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Year: 2014 PMID： 24954133 PMCID： PMC4441014 DOI： 10.1016/j.ccr.2014.05.005
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743