title: Spheres derived from the human SN12C renal cell carcinoma cell line are enriched in tumor initiating cells.
abstract: Recently, tumor initiating cells (TICs), which possess self-renewal and other stem cell properties, are regarded as the cause of tumor initiation, recurrence and metastasis. The isolation and identification of TICs could help to develop novel therapeutic strategies.
  
  
  
  In this study, we isolated spheroid cells from human renal cell carcinoma (RCC) cell line SN12C in stem cell-conditioned medium. The stemness characteristics of spheroid cells, including tumorigenicity, self-renewal, proliferation and aldehyde dehydrogenase (ALDH) activity were evaluated; the expression levels of stemness genes and related proteins were assessed. Furthermore, study examined the differentiation of TICs into endothelial cells and the relationship between TICs and EMT.
  
  
  
  Our data demonstrated that spheroid cells cultured in defined serum-free medium possessed TIC properties, such as high tumorigenic capacity, upregulation of TIC-related genes and proteins, persistent self-renewal and extensive proliferation. Furthermore, spheroid cells were more aggressive in growth, invasion, scratch recovery, clonogenic survival and high aldehyde dehydrogenase (ALDH) activity. Interestingly, a marked increase in tumor vascularity compared to adherent tumors in vivo, and spheroid cells can differentiate into functional endothelial-like cells in vitro suggesting a role of tumor initiating cells in tumor angiogenesis. The spheroid cells also demonstrated down-regulated E-cadherin and up-regulated Vimentin expression, which is the typical phenotype of EMT.
  
  
  
  These results suggest that spheroid cells with tumor initiating cells-like characteristics contributed to tumor generation, progression, high tumorigenicity, pro-angiogenic capability and relationship with EMT. Further experiments using more refined selection criteria such as a combination of two or multiple markers would be useful to specifically identify and purify TICs.
authors.affiliation: Department of Pathology, Tianjin Cancer Hospital, Tianjin Medical University, Tianjin, 300060, China.
authors.forename: Yanhui
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Tianjin Cancer Hospital, Tianjin Medical University, Tianjin, 300060, China. baocunsun@gmail.com.|Department of Pathology, Tianjin Medical University, Tianjin, 300070, China. baocunsun@gmail.com.|Department of Pathology, Tianjin General Hospital, Tianjin Medical University, Tianjin, 300052, China. baocunsun@gmail.com.
authors.forename: Baocun
authors.initials: B
authors.lastname: Sun
authors.affiliation: Department of Pathology, Tianjin Medical University, Tianjin, 300070, China.|Department of Pathology, Tianjin General Hospital, Tianjin Medical University, Tianjin, 300052, China.
authors.forename: Xiulan
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Pathology, Tianjin Medical University, Tianjin, 300070, China.
authors.forename: Huizhi
authors.initials: H
authors.lastname: Sun
authors.affiliation: Tianjin Third Central Hospital, Tianjin, 300170, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Cui
authors.affiliation: Department of Pathology, Tianjin Cancer Hospital, Tianjin Medical University, Tianjin, 300060, China.
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Pathology, Tianjin Cancer Hospital, Tianjin Medical University, Tianjin, 300060, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Yao
authors.affiliation: Department of Pathology, Tianjin Medical University, Tianjin, 300070, China.|Department of Pathology, Tianjin General Hospital, Tianjin Medical University, Tianjin, 300052, China.
authors.forename: Xueyi
authors.initials: X
authors.lastname: Dong
mesh_terms: D000444:Aldehyde Dehydrogenase / Q000378:metabolism; D000818:Animals; D002292:Carcinoma, Renal Cell / Q000378:metabolism / Q000473:pathology*; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D000066673:Cell Self Renewal; D058750:Epithelial-Mesenchymal Transition; D006801:Humans; D007680:Kidney Neoplasms / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D018874:Spheroids, Cellular / Q000166:cytology* / Q000378:metabolism / Q000473:pathology
chemical_list: D000444:Aldehyde Dehydrogenase
keywords: Angiogenesis; Renal cell carcinoma; Spheroid; Tumor initiating cells