title: CD133(+) gallbladder carcinoma cells exhibit self-renewal ability and tumorigenicity.
abstract: OBJECTIVE
  To identify cancer stem cells (CSCs) in human gallbladder carcinomas (GBCs).
  
  
  METHODS
  Primary GBC cells were cultured under serum-free conditions to produce floating spheres. The stem-cell properties of the sphere-forming cells, including self-renewal, differentiation potential, chemoresistance and tumorigenicity, were determined in vitro or in vivo. Cell surface expression of CD133 was investigated in primary tumors and in spheroid cells using flow cytometry. The sphere-colony-formation ability and tumorigenicity of CD133(+) cells were assayed.
  
  
  RESULTS
  In vitro culture experiments revealed that floating spheroids were generated from primary GBC cells, and these sphere-forming cells could generate new progeny spheroids in serum-free media. Spheroid cells were differentiated under serum-containing conditions with downregulation of the stem cell markers Oct-4, Nanog, and nestin (P < 0.05). The differentiated cells showed lower spheroid-colony-formation ability than the original spheroid cells (P < 0.05). Spheroid cells were more resistant to chemotherapeutic reagents than the congenetic adherent cells (P < 0.05). Flow cytometry showed enriched CD133(+) population in sphere-forming cells (P < 0.05). CD133(+) cells possessed high colony-formation ability than the CD133(-) population (P < 0.01). CD133(+) cells injected into nude mice revealed higher tumorigenicity than their antigen-negative counterparts (P < 0.05).
  
  
  CONCLUSIONS
  CD133 may be a cell surface marker for CSCs in GBC.
authors: Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China.
authors: Cheng-Jian
authors: CJ
authors: Shi
authors: Jun
authors: J
authors: Gao
authors: Min
authors: M
authors: Wang
authors: Xin
authors: X
authors: Wang
authors: Rui
authors: R
authors: Tian
authors: Feng
authors: F
authors: Zhu
authors: Ming
authors: M
authors: Shen
authors: Ren-Yi
authors: RY
authors: Qin
mesh_terms: D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D014408:Biomarkers, Tumor; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D005260:Female; D005706:Gallbladder Neoplasms / Q000378:metabolism* / Q000473:pathology*; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology*; D010455:Peptides / Q000378:metabolism*; D018874:Spheroids, Cellular / Q000166:cytology / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D014408:Biomarkers, Tumor; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse