Multipotent CD15+ Cancer Stem Cells in Patched-1-Deficient Mouse Medulloblastoma

被引:135
作者
Ward, Ryan J. [2 ,3 ]
Lee, Lilian [2 ]
Graham, Kevin [2 ]
Satkunendran, Thevagi [4 ]
Yoshikawa, Koichi [3 ]
Ling, Erick [2 ,3 ]
Harper, Lauren [2 ]
Austin, Ryan [2 ]
Nieuwenhuis, Erica
Clarke, Ian D. [2 ]
Hui, Chi-chung [4 ]
Dirks, Peter B. [1 ,2 ,3 ]
机构
[1] Hosp Sick Children, Div Neurosurg, Program Dev Biol, Toronto, ON M5G 1X8, Canada
[2] Univ Toronto, Arthur & Sonia Labatt Brain Tumor Res Ctr, Toronto, ON, Canada
[3] Univ Toronto, Dept Lab Med & Pathol, Toronto, ON, Canada
[4] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada
基金
加拿大健康研究院;
关键词
CENTRAL-NERVOUS-SYSTEM; PRIMITIVE NEUROECTODERMAL TUMORS; HUMAN HOMOLOG; BRAIN-TUMORS; PERIVASCULAR NICHE; INITIATING CELLS; SELF-RENEWAL; MUTATIONS; MICE; PATHWAY;
D O I
10.1158/0008-5472.CAN-09-0342
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Subpopulations of tumorigenic cells have been identified in many human tumors, although these cells may not be very rare in some types of cancer. Here, we report that medulloblastomas arising from Patched-1-deficient mice contain a subpopulation of cells that show a neural precursor phenotype, clonogenic and multilineage differentiation capacity, activated Hedgehog signaling, wild-type Patched-1 expression, and the ability to initiate tumors following allogeneic orthotopic transplantation. The normal neural stem cell surface antigen CD15 enriches for the in vitro proliferative and in vivo tumorigenic potential from uncultured medullo-blastomas, supporting the existence of a cancer stem cell hierarchy in this clinically relevant mouse model of cancer. [Cancer Res 2009;69(11):4682-90]
引用
收藏
页码:4682 / 4690
页数:9
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