Identification of CD15 as a marker for tumor-propagating cells in a mouse model of medulloblastoma

Cancer Cell. 2009 Feb 3;15(2):135-47. doi: 10.1016/j.ccr.2008.12.016.

Abstract

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 propagated not 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • AC133 Antigen
  • Animals
  • Antigens, CD / metabolism
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Biomarkers, Tumor*
  • Brain Neoplasms* / pathology
  • Brain Neoplasms* / physiopathology
  • Disease Models, Animal
  • Gene Expression Profiling
  • Glycoproteins / metabolism
  • Hedgehog Proteins / genetics
  • Hedgehog Proteins / metabolism
  • Humans
  • Lewis X Antigen / genetics
  • Lewis X Antigen / metabolism*
  • Medulloblastoma* / pathology
  • Medulloblastoma* / physiopathology
  • Mice
  • Mice, Mutant Strains
  • Mice, SCID
  • Microarray Analysis
  • Molecular Sequence Data
  • Neoplasm Transplantation
  • Neoplastic Stem Cells* / metabolism
  • Neoplastic Stem Cells* / pathology
  • Neurons / cytology
  • Neurons / metabolism
  • Patched Receptors
  • Peptides / metabolism
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Signal Transduction / physiology
  • Stem Cells / cytology
  • Stem Cells / metabolism
  • Survival Rate
  • Tumor Cells, Cultured

Substances

  • AC133 Antigen
  • Antigens, CD
  • Atoh1 protein, mouse
  • Basic Helix-Loop-Helix Transcription Factors
  • Biomarkers, Tumor
  • Glycoproteins
  • Hedgehog Proteins
  • Lewis X Antigen
  • PROM1 protein, human
  • Patched Receptors
  • Peptides
  • Prom1 protein, mouse
  • Receptors, Cell Surface
  • Recombinant Fusion Proteins

Associated data

  • GEO/GSE12430