Cancer stem cell-like characteristics of a CD133+ subpopulation in the J82 human bladder cancer cell line

摘要

Cancer stem cells (CSCs) are thought to be crucial for understanding the biological roots of cancer, and are of increasing importance as a target for new anticancer agents. According to an expression analysis of the cell surface antigens of various types of cancer, CD133 is considered to be a potential marker of cancer stemness. In this study, a human urinary bladder cancer cell line (J82) was used to analyze the cancer stem cell-like characteristics of CD133⁺ bladder cancer cells in vitro and in vivo. The CD133 expression in the J82 cells was examined and the cells were immunomagnetically categorized into positive and negative subsets. The CD133⁻ and CD133⁺ subsets were phenotypically divergent with regard to the cell growth pattern, while CD133⁺ cells tended to colonize during their growth. In CD133⁺ cells, the pluripotent stem cell factors Oct-4 and Sox-2 were upregulated, and a statistically significant proliferation increase was observed when compared to CD133⁻ cells. The CD133⁺ subpopulation was more tolerant to the chemotherapeutic agent cisplatin, and Bacillus Calmette-Guérin (BCG), an agent instilled intravesically to treat bladder cancer. In addition, CD133⁺ J82 cells were more resistant to radiation treatment when compared to CD133⁻ cells. The in vivo tumorigenesis of the CD133⁻ and CD133⁺ subsets of J82 cancer cells was also examined by subcutaneously injecting them into nude mice. The tumor growth was more aggressive in the CD133⁺ subpopulation, showing a significant difference in the tumorigenic potential in these subsets. In conclusion, J82 human bladder cancer cells include CD133⁻ and CD133⁺ subpopulations, while the CD133 molecule is a potential marker of the potential malignancy of human bladder cancer. In the present study, the CD133⁺ subpopulation was herein demonstrated to have certain characteristics consistent with those of cancer stem cells.