This Article Full Text Full Text (PDF) Supplementary Data Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Ward, R. J. Articles by Dirks, P. B. PubMed PubMed Citation Articles by Ward, R. J. Articles by Dirks, P. B.

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

¹ Developmental and Stem Cell Biology, Hospital for Sick Children; ² Arthur and Sonia Labatt Brain Tumor Research Center and Departments of ³ Laboratory Medicine and Pathobiology and ⁴ Molecular Genetics, University of Toronto, Toronto, Ontario, Canada

Requests for reprints: Peter B. Dirks, Division of Neurosurgery/Program in Developmental Biology, Hospital for Sick Children, Suite 1503, 555 University Avenue, Toronto, ON, Canada M5G 1X8. Phone: 416-813-8529; Fax: 416-813-5252; E-mail: peter.dirks{at}sickkids.ca.

Key Words: Cancer Stem Cells • Patched-1 Medulloblastoma • Hedgehog Signaling • Brain Tumor • CD15

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. [Cancer Res 2009;69(11):4682–90]