Multipotent CD15+ cancer stem cells in patched-1-deficient mouse medulloblastoma.
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 medulloblastomas, supporting the existence of a cancer stem cell hierarchy in this clinically relevant mouse model of cancer.
Ward
Ryan J
RJ
Developmental and Stem Cell Biology, Hospital for Sick Children, ON, Canada M5G 1X8.
Lee
Lilian
L
Graham
Kevin
K
Satkunendran
Thevagi
T
Yoshikawa
Koichi
K
Ling
Erick
E
Harper
Lauren
L
Austin
Ryan
R
Nieuwenhuis
Erica
E
Clarke
Ian D
ID
Hui
Chi-Chung
CC
Dirks
Peter B
PB
D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002528:Cerebellar Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D004622:Embryo, Mammalian; D005647:Fucosyltransferases / Q000378:metabolism; D016256:Lewis X Antigen / Q000378:metabolism*; D008527:Medulloblastoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008822:Mice, Transgenic; D008954:Models, Biological; D039902:Multipotent Stem Cells / Q000378:metabolism / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D010641:Phenotype; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000378:metabolism
D016256:Lewis X Antigen; C000606236:PTCH1 protein, human; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; C000606240:Ptch1 protein, mouse; D011956:Receptors, Cell Surface; D005647:Fucosyltransferases; C541914:Fut4 protein, mouse