Portal de Periódicos da CAPES

Quiescent Sox2+ Cells Drive Hierarchical Growth and Relapse in Sonic Hedgehog Subgroup Medulloblastoma

2014; Cell Press; Volume: 26; Issue: 1 Linguagem: Inglês

10.1016/j.ccr.2014.05.005

1878-3686

Robert J. Vanner, Marc Remke, Marco Gallo, Hayden Selvadurai, Fiona J. Coutinho, Lilian Lee, Michelle Kushida, Renee Head, A. Sorana Morrissy, Xueming Zhu, Tzvi Aviv, Véronique Voisin, Ian D. Clarke, Yisu Li, Andrew J. Mungall, Richard A. Moore, Yussanne Ma, Steven J.M. Jones, Marco A. Marra, David Malkin, Paul A. Northcott, Marcel Kool, Stefan M. Pfister, Gary D. Bader, Konrad Hochedlinger, Andrey Korshunov, Michael D. Taylor, Peter B. Dirks,

Glioma Diagnosis and Treatment

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.