摘要
髓母细胞瘤和其他胚胎性脑肿瘤在形态和分化上同神经干细胞和祖细胞相似。通过人类肿瘤标本的基因表达研究和转基因鼠模型分析,提示多能外胚层小脑干细胞和谱系限制性的祖细胞可以通过基因的改变转化为髓母细胞瘤。这些分子的改变常常涉及到Wnt、Hedgehog和Notch等信号通路的组成性激活,这些信号通路在非肿瘤性神经干细胞中发挥重要作用。通过药物阻断Hedgehog和Notch信号通路在体外培养和体内均可抑制髓母细胞瘤的生长,这个可以证明对于肿瘤的发生和长期增殖所必须的小肿瘤干细胞亚群以上述信号通路为靶点阻滞是有效的。
Medulloblastoma and other embronal brain tumors are similar in appearance and differentiation potential to neural stem and progenitor cells. Expression studies performed using human tumor samples, as well as the analysis of murine transgenic models, suggest that both muhipotent cerebellar stem cells and lineage-restricted progenitors of the external germinal layer can be transformed into medulloblastoma by genetic alterations. These molecular changes frequendy involve constitutive activation of signaling pathways such as Wnt, Hedgehog, and Notch, which play a key role in non-neoplastic neural stem cells. Pharmacologic blockade of the Hedgehog and Notch pathways suppresses the growth of medulloblastoma in culture and in vivo and may prove effective in targeting the small cancer stem-cell subpopulation required for tumor initiation and long-term propagation.
出处
《中国神经肿瘤杂志》
2009年第4期301-310,共10页
Chinese Journal of Neuro-Oncology
关键词
髓母细胞瘤
干细胞
Medulloblastoma
Stem cells
