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Oncotarget. 2017 Feb 28;8(9):15593-15609. doi: 10.18632/oncotarget.14777.

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.

Author information

1
Division of Uro-oncology, Department of Surgery, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
2
Department of Medical Research and Development, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
3
Cancer Center, Taipei Medical University-Shuang Ho Hospital, Taipei, Taiwan.
4
Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
5
School of Medicine, Chang Gung University, Taoyuan, Taiwan.
6
Graduate Institute of Clinical Medical Sciences, Chang Gung University, Taoyuan, Taiwan.
7
Department of Medical Science and College of Medicine, Tzu-Chi University, and Department of Internal Medicine, Tzu-Chji General Hospital, Hua-lien, Taiwan.
8
The Ph.D. Program for Cancer Biology and Drug Discovery, Taipei Medical University, Taipei, Taiwan.
9
Vectorite Biomedica Inc., Taipei, Taiwan.

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.

KEYWORDS:

CD24; CD44; cancer stem cells; epithelioid and fibroblastoid subsets; sarcomatoid renal cell carcinoma

PMID:
28121626
PMCID:
PMC5362508
DOI:
10.18632/oncotarget.14777
[Indexed for MEDLINE]
Free PMC Article

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