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CD133 expression is not restricted to stem cells, and both CD133+ and CD133- metastatic colon cancer cells initiate tumors.

Colon cancer stem cells are believed to originate from a rare population of putative CD133+ intestinal stem cells. Recent publications suggest that a small subset of colon cancer cells expresses CD133, and that only these CD133+ cancer cells are capable of tumor initiation. However, the precise contribution of CD133+ tumor-initiating cells in mediating colon cancer metastasis remains unknown. Therefore, to temporally and spatially track the expression of CD133 in adult mice and during tumorigenesis, we generated a knockin lacZ reporter mouse (CD133lacZ/+), in which the expression of lacZ is driven by the endogenous CD133 promoters. Using this model and immunostaining, we discovered that CD133 expression in colon is not restricted to stem cells; on the contrary, CD133 is ubiquitously expressed on differentiated colonic epithelium in both adult mice and humans. Using Il10-/-CD133lacZ mice, in which chronic inflammation in colon leads to adenocarcinomas, we demonstrated that CD133 is expressed on a full gamut of colonic tumor cells, which express epithelial cell adhesion molecule (EpCAM). Similarly, CD133 is widely expressed by human primary colon cancer epithelial cells, whereas the CD133- population is composed mostly of stromal and inflammatory cells. Conversely, CD133 expression does not identify the entire population of epithelial and tumor-initiating cells in human metastatic colon cancer. Indeed, both CD133+ and CD133- metastatic tumor subpopulations formed colonospheres in in vitro cultures and were capable of long-term tumorigenesis in a NOD/SCID serial xenotransplantation model. Moreover, metastatic CD133- cells form more aggressive tumors and express typical phenotypic markers of cancer-initiating cells, including CD44 (CD44+CD24-), whereas the CD133+ fraction is composed of CD44lowCD24+ cells. Collectively, our data suggest that CD133 expression is not restricted to intestinal stem or cancer-initiating cells, and during the metastatic transition, CD133+ tumor cells might give rise to the more aggressive CD133(- )subset, which is also capable of tumor initiation in NOD/SCID mice.

Pubmed ID: 18497886


  • Shmelkov SV
  • Butler JM
  • Hooper AT
  • Hormigo A
  • Kushner J
  • Milde T
  • St Clair R
  • Baljevic M
  • White I
  • Jin DK
  • Chadburn A
  • Murphy AJ
  • Valenzuela DM
  • Gale NW
  • Thurston G
  • Yancopoulos GD
  • D'Angelica M
  • Kemeny N
  • Lyden D
  • Rafii S


The Journal of clinical investigation

Publication Data

June 4, 2008

Associated Grants

  • Agency: NHLBI NIH HHS, Id: HL059312
  • Agency: NHLBI NIH HHS, Id: HL075234
  • Agency: NHLBI NIH HHS, Id: HL084936
  • Agency: Howard Hughes Medical Institute, Id:
  • Agency: Howard Hughes Medical Institute, Id:

Mesh Terms

  • Animals
  • Antigens, CD
  • Colonic Neoplasms
  • Epithelial Cells
  • Gene Expression Regulation, Neoplastic
  • Glycoproteins
  • Inflammation
  • Mice
  • Mice, SCID
  • Mice, Transgenic
  • Models, Biological
  • Models, Genetic
  • Neoplasm Metastasis
  • Peptides
  • Phenotype
  • Promoter Regions, Genetic
  • Stem Cells