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Identification of CD24 as a cancer stem cell marker in human nasopharyngeal carcinoma.

Yang CH, Wang HL, Lin YS, Kumar KP, Lin HC, Chang CJ, Lu CC, Huang TT, Martel J, Ojcius DM, Chang YS, Young JD, Lai HC - PLoS ONE (2014)

Bottom Line: In this study, we show that CD24+ cells isolated from human NPC cell lines express stem cell genes (Sox2, Oct4, Nanog, Bmi-1, and Rex-1), and show activation of the Wnt/β-catenin signaling pathway.CD24+ cells further show increased invasion ability in vitro, which correlates with enhanced expression of matrix metalloproteinase 2 and 9.In summary, our results suggest that CD24 represents a novel CSC biomarker in NPC.

View Article: PubMed Central - PubMed

Affiliation: Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan, Republic of China; Division of Applied Toxicology, Taiwan Agricultural Chemicals and Toxic Substances Research Institute, Council of Agriculture, Executive Yuan, Taichung, Taiwan, Republic of China.

ABSTRACT
Cancer stem cells (CSCs) represent a unique sub-population of tumor cells with the ability to initiate tumor growth and sustain self-renewal. Although CSC biomarkers have been described for various tumors, only a few markers have been identified for nasopharyngeal carcinoma (NPC). In this study, we show that CD24+ cells isolated from human NPC cell lines express stem cell genes (Sox2, Oct4, Nanog, Bmi-1, and Rex-1), and show activation of the Wnt/β-catenin signaling pathway. CD24+ cells possess typical CSC characteristics that include enhanced cell proliferation, increased colony and sphere formation, maintenance of cell differentiation potential in prolonged culture, and enhanced resistance to chemotherapeutic drugs. Notably, CD24+ cells produce tumors following inoculation of as few as 500 cells in immunodeficient NOD/SCID mice. CD24+ cells further show increased invasion ability in vitro, which correlates with enhanced expression of matrix metalloproteinase 2 and 9. In summary, our results suggest that CD24 represents a novel CSC biomarker in NPC.

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Expression levels of stem cell genes and activation of the Wnt/β-catenin pathway in CD24+ cells.(A) mRNA expression levels of Sox2, Oct4, Nanog, Bmi-1 and Rex-1 in parental, CD24+ and CD24− cells from the NPC cell lines, TW02 (left) and TW04 (right), was evaluated using quantitative RT-PCR analysis. The results shown represented the average of three independent experiments. *: p<0.05, **: p<0.01. (B) Western blots analysis of phosphorylated-GSK, GSK, phosphorylated-β-catenin, β-catenin and β-actin in whole cell lysates, and of β-catenin and lamin B1 in nuclear fractions of parental, CD24+, and CD24− cells isolated from the TW02 and TW04 cell lines. Quantitative result was calculated by ImageJ software. *: p<0.05, **: p<0.01, ***: p<0.001.
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pone-0099412-g002: Expression levels of stem cell genes and activation of the Wnt/β-catenin pathway in CD24+ cells.(A) mRNA expression levels of Sox2, Oct4, Nanog, Bmi-1 and Rex-1 in parental, CD24+ and CD24− cells from the NPC cell lines, TW02 (left) and TW04 (right), was evaluated using quantitative RT-PCR analysis. The results shown represented the average of three independent experiments. *: p<0.05, **: p<0.01. (B) Western blots analysis of phosphorylated-GSK, GSK, phosphorylated-β-catenin, β-catenin and β-actin in whole cell lysates, and of β-catenin and lamin B1 in nuclear fractions of parental, CD24+, and CD24− cells isolated from the TW02 and TW04 cell lines. Quantitative result was calculated by ImageJ software. *: p<0.05, **: p<0.01, ***: p<0.001.

Mentions: To examine whether CD24+ cells have intrinsic stem cell properties, we analyzed the expression of five embryonic stem cell genes (Sox2[27], Oct4[28]–[30], Nanog[31], Bmi-1[32], and Rex-1[33]) in TW02 and TW04 cell lines which were used as representative NPC cells. As indicated in Figure 2A, CD24+ cells consistently expressed higher levels of the five stem cell genes than parental or CD24− cells.


Identification of CD24 as a cancer stem cell marker in human nasopharyngeal carcinoma.

Yang CH, Wang HL, Lin YS, Kumar KP, Lin HC, Chang CJ, Lu CC, Huang TT, Martel J, Ojcius DM, Chang YS, Young JD, Lai HC - PLoS ONE (2014)

Expression levels of stem cell genes and activation of the Wnt/β-catenin pathway in CD24+ cells.(A) mRNA expression levels of Sox2, Oct4, Nanog, Bmi-1 and Rex-1 in parental, CD24+ and CD24− cells from the NPC cell lines, TW02 (left) and TW04 (right), was evaluated using quantitative RT-PCR analysis. The results shown represented the average of three independent experiments. *: p<0.05, **: p<0.01. (B) Western blots analysis of phosphorylated-GSK, GSK, phosphorylated-β-catenin, β-catenin and β-actin in whole cell lysates, and of β-catenin and lamin B1 in nuclear fractions of parental, CD24+, and CD24− cells isolated from the TW02 and TW04 cell lines. Quantitative result was calculated by ImageJ software. *: p<0.05, **: p<0.01, ***: p<0.001.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4067285&req=5

pone-0099412-g002: Expression levels of stem cell genes and activation of the Wnt/β-catenin pathway in CD24+ cells.(A) mRNA expression levels of Sox2, Oct4, Nanog, Bmi-1 and Rex-1 in parental, CD24+ and CD24− cells from the NPC cell lines, TW02 (left) and TW04 (right), was evaluated using quantitative RT-PCR analysis. The results shown represented the average of three independent experiments. *: p<0.05, **: p<0.01. (B) Western blots analysis of phosphorylated-GSK, GSK, phosphorylated-β-catenin, β-catenin and β-actin in whole cell lysates, and of β-catenin and lamin B1 in nuclear fractions of parental, CD24+, and CD24− cells isolated from the TW02 and TW04 cell lines. Quantitative result was calculated by ImageJ software. *: p<0.05, **: p<0.01, ***: p<0.001.
Mentions: To examine whether CD24+ cells have intrinsic stem cell properties, we analyzed the expression of five embryonic stem cell genes (Sox2[27], Oct4[28]–[30], Nanog[31], Bmi-1[32], and Rex-1[33]) in TW02 and TW04 cell lines which were used as representative NPC cells. As indicated in Figure 2A, CD24+ cells consistently expressed higher levels of the five stem cell genes than parental or CD24− cells.

Bottom Line: In this study, we show that CD24+ cells isolated from human NPC cell lines express stem cell genes (Sox2, Oct4, Nanog, Bmi-1, and Rex-1), and show activation of the Wnt/β-catenin signaling pathway.CD24+ cells further show increased invasion ability in vitro, which correlates with enhanced expression of matrix metalloproteinase 2 and 9.In summary, our results suggest that CD24 represents a novel CSC biomarker in NPC.

View Article: PubMed Central - PubMed

Affiliation: Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan, Republic of China; Division of Applied Toxicology, Taiwan Agricultural Chemicals and Toxic Substances Research Institute, Council of Agriculture, Executive Yuan, Taichung, Taiwan, Republic of China.

ABSTRACT
Cancer stem cells (CSCs) represent a unique sub-population of tumor cells with the ability to initiate tumor growth and sustain self-renewal. Although CSC biomarkers have been described for various tumors, only a few markers have been identified for nasopharyngeal carcinoma (NPC). In this study, we show that CD24+ cells isolated from human NPC cell lines express stem cell genes (Sox2, Oct4, Nanog, Bmi-1, and Rex-1), and show activation of the Wnt/β-catenin signaling pathway. CD24+ cells possess typical CSC characteristics that include enhanced cell proliferation, increased colony and sphere formation, maintenance of cell differentiation potential in prolonged culture, and enhanced resistance to chemotherapeutic drugs. Notably, CD24+ cells produce tumors following inoculation of as few as 500 cells in immunodeficient NOD/SCID mice. CD24+ cells further show increased invasion ability in vitro, which correlates with enhanced expression of matrix metalloproteinase 2 and 9. In summary, our results suggest that CD24 represents a novel CSC biomarker in NPC.

Show MeSH
Related in: MedlinePlus