Cancer stem/progenitor cells are highly enriched in CD133+CD44+ population in hepatocellular carcinoma

Int J Cancer. 2010 May 1;126(9):2067-78. doi: 10.1002/ijc.24868.


Both our previous study and other reports have suggested that CD133, originally classified as a hematopoietic stem cell marker, could be used for enrichment of cancer stem cells (CSCs) in human hepatocellular carcinoma (HCC). It was also noted that not all of CD133(+) cells were representative of CSCs. Further identification and characterization of CSCs or tumor-initiating cells in HCC are necessary to better understand hepatocarcinogenesis. In present study, we demonstrated that CSC phenotype could be precisely defined by co-expression of CD133 and CD44 cell surface markers. CD133(+)CD44(+) HCC cells showed stem cell properties, including extensive proliferation, self-renewal, and differentiation into the bulk of cancer cells. In vivo xenograft experiments revealed that, actually, the highly tumorigenic capacity of CD133(+) cells as previously described was primarily attributed to CD133(+)CD44(+) cell subpopulation, instead of their CD133(+)CD44(-) counterparts. Moreover, cells double-positive for CD133 and CD44 exhibited preferential expression of some stem cell-associated genes and were more resistant to chemotherapeutic agents due to the upregulation of ATP-binding cassette (ABC) superfamily transporters, including ABCB1, ABCC1, and ABCG2, further supporting these cells as HCC cell origin. Our findings suggest that CD133(+)CD44(+) cells might represent true cancer stem/progenitor cells in HCC, which could allow a better understanding of HCC initiation and progression, as well as establish a precise target for the development of more effective therapies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AC133 Antigen
  • ATP-Binding Cassette Transporters / analysis
  • Animals
  • Antigens, CD / analysis*
  • Carcinoma, Hepatocellular / pathology*
  • Cell Line, Tumor
  • Glycoproteins / analysis*
  • Humans
  • Hyaluronan Receptors / analysis*
  • Liver Neoplasms / pathology*
  • Male
  • Mice
  • Mice, SCID
  • Neoplastic Stem Cells / chemistry*
  • Neoplastic Stem Cells / drug effects
  • Peptides / analysis*


  • AC133 Antigen
  • ATP-Binding Cassette Transporters
  • Antigens, CD
  • CD44 protein, human
  • Glycoproteins
  • Hyaluronan Receptors
  • PROM1 protein, human
  • Peptides
  • Prom1 protein, mouse