CD133(-) cells, derived from a single human colon cancer cell line, are more resistant to 5-fluorouracil (FU) than CD133(+) cells, dependent on the β1-integrin signaling

J Surg Res. 2012 Jun 15;175(2):278-88. doi: 10.1016/j.jss.2011.03.076. Epub 2011 Apr 24.


Background and aim: Recently, the cancer stem cells (CSCs) theory has been proposed, and CD133 has been suggested as a potential marker of CSCs in various cancer types. In the present study, we aimed evaluate CD133 as a potential marker of colorectal CSCs and, for this purpose, isolated CD133(+) and CD133(-) cells from a single colorectal cancer cell line, and compared their features, especially related to the tumor-forming and differentiation abilities, and the sensitivity to chemotherapy.

Methods and results: CD133(+) cells had higher in vivo tumor-forming ability than CD133(-) cells, and in culture, they progressively differentiated into CD133(-) cells, but not vice-versa. On the other hand, CD133(-) cells were more resistant to 5-fluorouracil (FU) treatment than CD133(+) cells, and it was found to be dependent on the higher expression of ß1-integrins, and consequently, higher ability to bind collagen. Disruption of the ß1-integrin function abrogated the chemoresistance.

Conclusion: From the present results, we concluded that colorectal cancer CD133(+) cells, although showing some features of CSCs, are not more resistant to 5-FU than CD133(-) cells. Therefore, definite conclusions can not be drawn yet, but it is strongly suggestive that CD133 should not be used as a single CSC marker of colorectal cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AC133 Antigen
  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / immunology
  • Adenocarcinoma / physiopathology
  • Antigens, CD / genetics
  • Antigens, CD / metabolism*
  • Antimetabolites, Antineoplastic / therapeutic use
  • Apoptosis / physiology
  • Biomarkers, Tumor / immunology
  • Cell Line, Tumor
  • Cell Movement / physiology
  • Cell Transformation, Neoplastic / immunology
  • Cell Transformation, Neoplastic / pathology
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / immunology
  • Colorectal Neoplasms / physiopathology
  • Drug Resistance, Neoplasm / immunology*
  • Fluorouracil / therapeutic use*
  • Glycoproteins / deficiency*
  • Glycoproteins / genetics
  • Glycoproteins / metabolism*
  • Humans
  • Integrin beta1 / physiology*
  • Peptides / deficiency*
  • Peptides / genetics
  • Peptides / metabolism*
  • Signal Transduction / physiology*
  • Treatment Outcome


  • AC133 Antigen
  • Antigens, CD
  • Antimetabolites, Antineoplastic
  • Biomarkers, Tumor
  • Glycoproteins
  • Integrin beta1
  • PROM1 protein, human
  • Peptides
  • Fluorouracil