Oncotarget

Research Papers:

Differential expression of CD44 and CD24 markers discriminates the epitheliod from the fibroblastoid subset in a sarcomatoid renal carcinoma cell line: evidence suggesting the existence of cancer stem cells in both subsets as studied with sorted cells

Chin-Hsuan Hsieh, Shih-Chieh Hsiung, Chi-Tai Yeh, Chih-Feng Yen, Yah-Huei Wu Chou, Wei-Yi Lei, See-Tong Pang, Cheng-Keng Chuang _ and Shuen-Kuei Liao

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Oncotarget. 2017; 8:15593-15609. https://doi.org/10.18632/oncotarget.14777

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Abstract

Chin-Hsuan Hsieh1,2, Shih-Chieh Hsiung1, Chi-Tai Yeh4, Chih-Feng Yen3,5,6, Yah-Huei Wu Chou2, Wei-Yi Lei7, See-Tong Pang1,5, Cheng-Keng Chuang1,5,6, Shuen-Kuei Liao8,9

1Division of Uro-oncology, Department of Surgery, Chang Gung Memorial Hospital, Taoyuan, Taiwan

2Department of Medical Research and Development, Chang Gung Memorial Hospital, Taoyuan, Taiwan

3Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Taoyuan, Taiwan

4Cancer Center, Taipei Medical University-Shuang Ho Hospital, Taipei, Taiwan

5School of Medicine, Chang Gung University, Taoyuan, Taiwan

6Graduate Institute of Clinical Medical Sciences, Chang Gung University, Taoyuan, Taiwan

7Department of Medical Science and College of Medicine, Tzu-Chi University, and Department of Internal Medicine, Tzu-Chji General Hospital, Hua-lien, Taiwan

8The Ph.D. Program for Cancer Biology and Drug Discovery, Taipei Medical University, Taipei, Taiwan

9Vectorite Biomedica Inc., Taipei, Taiwan

Correspondence to:

Cheng-Keng Chuang, email: [email protected]

Shuen-Kuei Liao, email: [email protected]

Keywords: cancer stem cells, sarcomatoid renal cell carcinoma, epithelioid and fibroblastoid subsets, CD24, CD44

Received: May 30, 2016    Accepted: December 21, 2016    Published: January 21, 2017

ABSTRACT

Epithelioid and fibroblastoid subsets coexist in the human sarcomatoid renal cell carcinoma (sRCC) cell line, RCC52, according to previous clonal studies. Herein, using monoclonal antibodies to CD44 and CD24 markers, we identified and isolated these two populations, and showed that CD44bright/CD24dim and CD44bright/CD24bright phenotypes correspond to epithelioid and fibroblastoid subsets, respectively. Both sorted subsets displayed different levels of tumorigenicity in xenotransplantation, indicating that each harbored its own cancer stem cells (CSCs). The CD44bright/CD24bright subset, associated with higher expression of MMP-7, -8 and TIMP-1 transcripts, showed greater migratory/invasive potential than the CD44bright/CD24dim subset, which was associated with higher expression of MMP-2, -9 and TIMP-2 transcripts. Both subsets differentially expressed stemness gene products c-Myc, Oct4A, Notch1, Notch2 and Notch3, and the RCC stem cell marker, CD105 in 4-5% of RCC52 cells. These results suggest the presence of CSCs in both sRCC subsets for the first time and should therefore be considered potential therapeutic targets for this aggressive malignancy.


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