Cancer stem/progenitor cells are highly enriched in CD133+CD44+ population in hepatocellular carcinoma.
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.
Zhu
Zheng
Z
Shanghai Medical College, Fudan University, Shanghai, China.
Hao
Xiangfang
X
Yan
Mingxia
M
Yao
Ming
M
Ge
Chao
C
Gu
Jianren
J
Li
Jinjun
J
D000071916:AC133 Antigen; D018528:ATP-Binding Cassette Transporters / Q000032:analysis; D000818:Animals; D015703:Antigens, CD / Q000032:analysis*; D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D045744:Cell Line, Tumor; D006023:Glycoproteins / Q000032:analysis*; D006801:Humans; D018960:Hyaluronan Receptors / Q000032:analysis*; D008113:Liver Neoplasms / Q000473:pathology*; D008297:Male; D051379:Mice; D016513:Mice, SCID; D014411:Neoplastic Stem Cells / Q000737:chemistry* / Q000187:drug effects; D010455:Peptides / Q000032:analysis*
D000071916:AC133 Antigen; D018528:ATP-Binding Cassette Transporters; D015703:Antigens, CD; C497483:CD44 protein, human; D006023:Glycoproteins; D018960:Hyaluronan Receptors; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse