• Register
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.


Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.


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