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
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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AC133 Antigen
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Animals
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Antigens, CD / metabolism
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Basic Helix-Loop-Helix Transcription Factors / genetics
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Basic Helix-Loop-Helix Transcription Factors / metabolism
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Biomarkers, Tumor*
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Brain Neoplasms* / pathology
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Brain Neoplasms* / physiopathology
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Disease Models, Animal
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Gene Expression Profiling
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Glycoproteins / metabolism
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Hedgehog Proteins / genetics
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Hedgehog Proteins / metabolism
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Humans
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Lewis X Antigen / genetics
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Lewis X Antigen / metabolism*
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Medulloblastoma* / pathology
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Medulloblastoma* / physiopathology
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Mice
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Mice, Mutant Strains
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Mice, SCID
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Microarray Analysis
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Molecular Sequence Data
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Neoplasm Transplantation
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Neoplastic Stem Cells* / metabolism
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Neoplastic Stem Cells* / pathology
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Neurons / cytology
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Neurons / metabolism
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Patched Receptors
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Peptides / metabolism
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Receptors, Cell Surface / genetics
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Receptors, Cell Surface / metabolism
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
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Signal Transduction / physiology
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Stem Cells / cytology
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Stem Cells / metabolism
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Survival Rate
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Tumor Cells, Cultured
Substances
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AC133 Antigen
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Antigens, CD
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Atoh1 protein, mouse
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Basic Helix-Loop-Helix Transcription Factors
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Biomarkers, Tumor
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Glycoproteins
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Hedgehog Proteins
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Lewis X Antigen
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PROM1 protein, human
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Patched Receptors
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Peptides
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Prom1 protein, mouse
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Receptors, Cell Surface
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Recombinant Fusion Proteins