title: 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.
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.
authors.affiliation: Division of Uro-oncology, Department of Surgery, Chang Gung Memorial Hospital, Taoyuan, Taiwan.|Department of Medical Research and Development, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
authors.forename: Chin-Hsuan
authors.initials: CH
authors.lastname: Hsieh
authors.affiliation: Division of Uro-oncology, Department of Surgery, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
authors.forename: Shih-Chieh
authors.initials: SC
authors.lastname: Hsiung
authors.affiliation: Cancer Center, Taipei Medical University-Shuang Ho Hospital, Taipei, Taiwan.
authors.forename: Chi-Tai
authors.initials: CT
authors.lastname: Yeh
authors.affiliation: Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Taoyuan, Taiwan.|School of Medicine, Chang Gung University, Taoyuan, Taiwan.|Graduate Institute of Clinical Medical Sciences, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Chih-Feng
authors.initials: CF
authors.lastname: Yen
authors.affiliation: Department of Medical Research and Development, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
authors.forename: Yah-Huei Wu
authors.initials: YW
authors.lastname: Chou
authors.affiliation: Department of Medical Science and College of Medicine, Tzu-Chi University, and Department of Internal Medicine, Tzu-Chji General Hospital, Hua-lien, Taiwan.
authors.forename: Wei-Yi
authors.initials: WY
authors.lastname: Lei
authors.affiliation: Division of Uro-oncology, Department of Surgery, Chang Gung Memorial Hospital, Taoyuan, Taiwan.|School of Medicine, Chang Gung University, Taoyuan, Taiwan.
authors.forename: See-Tong
authors.initials: ST
authors.lastname: Pang
authors.affiliation: Division of Uro-oncology, Department of Surgery, Chang Gung Memorial Hospital, Taoyuan, Taiwan.|School of Medicine, Chang Gung University, Taoyuan, Taiwan.|Graduate Institute of Clinical Medical Sciences, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Cheng-Keng
authors.initials: CK
authors.lastname: Chuang
authors.affiliation: The Ph.D. Program for Cancer Biology and Drug Discovery, Taipei Medical University, Taipei, Taiwan.|Vectorite Biomedica Inc., Taipei, Taiwan.
authors.forename: Shuen-Kuei
authors.initials: SK
authors.lastname: Liao
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D051927:CD24 Antigen / Q000378:metabolism*; D000072645:Cancer-Associated Fibroblasts / Q000378:metabolism* / Q000473:pathology; D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D015622:Epithelioid Cells / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism*; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D020782:Matrix Metalloproteinases / Q000235:genetics; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology; D051880:Receptors, Notch / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019714:Tissue Inhibitor of Metalloproteinases / Q000235:genetics; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014183:Transplantation, Heterologous
chemical_list: D014408:Biomarkers, Tumor; D051927:CD24 Antigen; C497483:CD44 protein, human; D018960:Hyaluronan Receptors; D051880:Receptors, Notch; D019714:Tissue Inhibitor of Metalloproteinases; D053773:Transforming Growth Factor beta1; D020782:Matrix Metalloproteinases
keywords: CD24; CD44; cancer stem cells; epithelioid and fibroblastoid subsets; sarcomatoid renal cell carcinoma