Identification of CD15 as a Marker for Tumor-Propagating Cells in a Mouse Model of Medulloblastoma

The growth of many cancers depends on self-renewing cells called cancer stem cells or tumor-propagating cells (TPCs). In human brain tumors, cells expressing the stem cell marker CD133 have been implicated as TPCs. We show that tumors from a model of medulloblastoma, the Patched mutant mouse, are propagated not by CD133+ cells but by cells expressing the progenitor markers Math1 and CD15/SSEA-1. CD15 is also found in a subset of human medulloblastomas, and tumors expressing genes similar to those found in murine CD15+ cells have a poorer prognosis. Our data challenge the notion that all brain tumors are propagated by stem-like cells and raise the possibility that CD15 may be used to identify and target TPCs in human brain tumors.

Right: Cerebellum from an immunodeficient mouse (stained with DAPI to label all nuclei blue) transplanted with tumor-propagating cells from a patched mutant mouse with medulloblastoma. Two weeks after transplantation, cells (green) have begun to migrate from the injection site (middle of the field) to the surface of the cerebellum (left), where they will eventually form a tumor. The neuronal phenotype of these cells (indicated by their expression of the neuronal progenitor marker Math1-GFP) challenges the notion that all medulloblastomas are propagated by stem-like cells.

Read TA, Fogarty MP, Markant SL, McLendon RE, Wei Z, Ellison DW, Febbo PG and Wechsler-Reya RJ (2009) Identification of CD15 as a Marker for Tumor-Propagating Cells in a Mouse Model of Medulloblastoma. Cancer Cell. 15: 135-147.

Robert Wechsler-Reya
Associate Professor Pharmacology and Cancer Biology