Ballabio Claudio, Gianesello Matteo, Lago Chiara, Okonechnikov Konstantin, Anderle Marica, Aiello Giuseppe, Antonica Francesco, Zhang Tingting, Gianno Francesca, Giangaspero Felice, Hassan Bassem A, Pfister Stefan M, Tiberi Luca
Armenise-Harvard Laboratory of Brain Cancer, Department CIBIO, University of Trento, Via Sommarive 9, 38123 Trento, Italy.
Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.
Sci Adv. 2021 Jun 23;7(26). doi: 10.1126/sciadv.abd2781. Print 2021 Jun.
The identity of the cell of origin is a key determinant of cancer subtype, progression, and prognosis. Group 3 medulloblastoma (MB) is a malignant childhood brain cancer with poor prognosis and few candidates as putative cell of origin. We overexpressed the group 3 MB genetic drivers and in different candidate cells of origin in the postnatal mouse cerebellum. We found that S100b cells are competent to initiate group 3 MB, and we observed that S100b cells have higher levels of Notch1 pathway activity compared to Math1 cells. We found that additional activation of Notch1 in Math1 and Sox2 cells was sufficient to induce group 3 MB upon / expression. Together, our data suggest that the Notch1 pathway plays a critical role in group 3 MB initiation.
肿瘤起源细胞的身份是癌症亚型、进展和预后的关键决定因素。3组髓母细胞瘤（MB）是一种预后不良的儿童恶性脑癌，几乎没有候选的假定起源细胞。我们在出生后小鼠小脑的不同候选起源细胞中过表达了3组MB基因驱动因子。我们发现S100b细胞有能力引发3组MB，并且我们观察到与Math1细胞相比，S100b细胞具有更高水平的Notch1信号通路活性。我们发现，在Math1和Sox2细胞中额外激活Notch1足以在/表达时诱导3组MB。总之，我们的数据表明Notch1信号通路在3组MB的起始中起关键作用。
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