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

来源：

CANCER RESEARCH | 2009年 / 69卷 / 11期

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

页码：4682 / 4690

页数：9

共 48 条

[1] Glioma stem cells promote radioresistance by preferential activation of the DNA damage response [J].

Bao, Shideng ;

Wu, Qiulian ;

McLendon, Roger E. ;

Hao, Yueling ;

Shi, Qing ;

Hjelmeland, Anita B. ;

Dewhirst, Mark W. ;

Bigner, Darell D. ;

Rich, Jeremy N. .

NATURE, 2006, 444 (7120) :756-760

[2] Medulloblastoma growth inhibition by Hedgehog pathway blockade [J].

Berman, DM ;

Karhadkar, SS ;

Hallahan, AR ;

Pritchard, JI ;

Eberhart, CG ;

Watkins, DN ;

Chen, JK ;

Cooper, MK ;

Taipale, J ;

Olson, JM ;

Beachy, PA .

SCIENCE, 2002, 297 (5586) :1559-1561

[3] A perivascular niche for brain tumor stem cells [J].

Calabrese, Christopher ;

Poppleton, Helen ;

Kocak, Mehmet ;

Hogg, Twala L. ;

Fuller, Christine ;

Hamner, Blair ;

Oh, Eun Young ;

Gaber, M. Waleed ;

Finklestein, David ;

Allen, Meredith ;

Frank, Adrian ;

Bayazitov, Ildar T. ;

Zakharenko, Stanislav S. ;

Gajjar, Amar ;

Davidoff, Andrew ;

Gilbertson, Richard J. .

CANCER CELL, 2007, 11 (01) :69-82

[4] LeX/ssea-1 is expressed by adult mouse CNS stem cells, identifying them as nonependymal [J].

Capela, A ;

Temple, S .

NEURON, 2002, 35 (05) :865-875

[5] HEDGEHOG-GLI1 signaling regulates human glioma growth, cancer stem cell self-renewal, and tumorigenicity [J].

Clement, Virginie ;

Sanchez, Pilar ;

de Tribolet, Nicolas ;

Radovanovic, Ivan ;

Altaba, Ariel Ruiz I. .

CURRENT BIOLOGY, 2007, 17 (02) :165-172

[6] Niche-independent symmetrical self-renewal of a mammalian tissue stem cell [J].

Conti, L ;

Pollard, SM ;

Gorba, T ;

Reitano, E ;

Toselli, M ;

Biella, G ;

Sun, YR ;

Sanzone, S ;

Ying, QL ;

Cattaneo, E ;

Smith, A .

PLOS BIOLOGY, 2005, 3 (09) :1594-1606

[7]

delaPompa J, 1997, DEVELOPMENT, V124, P1139

[8] CANCER STEM CELLS Here, there, everywhere? [J].

Eaves, Connie J. .

NATURE, 2008, 456 (7222) :581-582

[9] Fibroblast growth factor blocks Sonic hedgehog signaling in neuronal precursors and tumor cells [J].

Fogarty, Marie P. ;

Emmenegger, Brian A. ;

Grasfeder, Linda L. ;

Oliver, Trudy G. ;

Wechsler-Reya, Robert J. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (08) :2973-2978

[10] The TP53-ARF tumor suppressor pathway is frequently disrupted in large/cell anaplastic medulloblastoma [J].

Frank, AJ ;

Hernan, R ;

Hollander, A ;

Lindsey, JC ;

Lusher, ME ;

Fuller, CE ;

Clifford, SC ;

Gilbertson, RJ .

MOLECULAR BRAIN RESEARCH, 2004, 121 (1-2) :137-140

← 1 2 3 4 5 →