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 1, 2 , Shih-Chieh Hsiung 1 , Chi-Tai Yeh 4 , Chih-Feng Yen 3, 5, 6 , Yah-Huei Wu Chou 2 , Wei-Yi Lei 7 , See-Tong Pang 1, 5 , Cheng-Keng Chuang 1, 5, 6 , Shuen-Kuei Liao 8, 9 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 Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Taoyuan, Taiwan 4 Cancer Center, Taipei Medical University-Shuang Ho Hospital, Taipei, 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 Correspondence to: Cheng-Keng Chuang, email: chuang89@cgmh.org.tw Shuen-Kuei Liao, email: liaosk@h.tmu.edu.tw 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 CD44 bright /CD24 dim and CD44 bright /CD24 bright 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 CD44 bright /CD24 bright subset, associated with higher expression of MMP-7, -8 and TIMP-1 transcripts, showed greater migratory/invasive potential than the CD44 bright /CD24 dim 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.