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

Abstract

Summary 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. Here we show that tumors from a model of medulloblastoma, the Patched mutant mouse, are not propagated by CD133+ cells but by cells expressing the progenitor markers Math1 and CD15/SSEA-1. These cells have a distinct expression profile that suggests increased proliferative capacity and decreased tendency to undergo apoptosis and differentiation. 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. Thus, CD15 may represent an important marker for TPCs in medulloblastoma. Significance Although tumor-propagating cells have been described in human brain tumors, such cells have not been identified in mouse models of the disease. Finding TPCs in mouse models is critical because it allows studies of their developmental origins, and experimental manipulation and targeting of these cells in a species-matched microenvironment. Here we identify a population of TPCs in a model of medulloblastoma, and show that these cells express CD15 (also known as SSEA-1 or LeX) and resemble neural progenitors. 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.