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Cancer stem/progenitor cells are highly enriched in CD133 + CD44 + population in hepatocellular carcinoma
Author(s) -
Zhu Zheng,
Hao Xiangfang,
Yan Mingxia,
Yao Ming,
Ge Chao,
Gu Jianren,
Li Jinjun
Publication year - 2009
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.24868
Subject(s) - cancer stem cell , cd44 , stem cell , cancer research , progenitor cell , side population , biology , stem cell marker , cancer cell , cancer , population , cell , microbiology and biotechnology , medicine , biochemistry , genetics , environmental health
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.