title: Tumor initiating cells in esophageal squamous cell carcinomas express high levels of CD44.
abstract: BACKGROUND
  Esophageal Squamous Cell Carcinoma (ESCC) is a major subtype of esophageal cancer causing significant morbility and mortality in Asia. Mechanism of initiation and progression of this disease is unclear. Tumor initiating cells (TICs) are the subpopulation of cells which have the ability to self-renew, as well as, to drive initiation and progression of cancer. Increasing evidence has shown that TICs exist in a variety of tumors. However, the identification and characterization of TICs in esophageal carcinoma has remained elusive.
  
  
  RESULTS
  to identify TICs in ESCC, ESCC cell lines including two primary cells were used for screening suitable surface marker. Then colony formation assay, drug resistant assay and tumorigenicity assay in immune deficient mice were used to characterize TICs in ESCC. We found that just the CD44 expression correlated with tumorigenicity in ESCC cell lines. And then induced differentiation of ESCC cells by all-trans retinoic acid treatment led to decreased expression of CD44. The FACS isolated cell subpopulations with high CD44 expression showed increased colony formation and drug resistance in vitro, as well as significantly enhanced tumorigenicity in NOD/SICD mice, as compared to the low expressing CD44 ESCC cells.
  
  
  CONCLUSIONS
  our study has discovered a novel TIC surface marker, CD44, which can be utilized to enrich efficiently the TICs in ESCC. These findings will be useful for further studies of these cells and exploring therapeutic approaches.
authors: Laboratory of Molecular Oncology, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Graduate School of Chinese Academy of Sciences, Shanghai, China.
authors: Jiang-Sha
authors: JS
authors: Zhao
authors: Wen-Jie
authors: WJ
authors: Li
authors: Di
authors: D
authors: Ge
authors: Pei-Jing
authors: PJ
authors: Zhang
authors: Jing-Jing
authors: JJ
authors: Li
authors: Chun-Lai
authors: CL
authors: Lu
authors: Xiao-Dan
authors: XD
authors: Ji
authors: Dong-Xian
authors: DX
authors: Guan
authors: Hong
authors: H
authors: Gao
authors: Li-Yan
authors: LY
authors: Xu
authors: Eng-Ming
authors: EM
authors: Li
authors: Harmik
authors: H
authors: Soukiasian
authors: H Phillip
authors: HP
authors: Koeffler
authors: Xiao-Fan
authors: XF
authors: Wang
authors: Dong
authors: D
authors: Xie
mesh_terms: D000328:Adult; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000473:pathology*; D016923:Cell Death / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000187:drug effects; D004938:Esophageal Neoplasms / Q000188:drug therapy / Q000473:pathology*; D005260:Female; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism*; D008297:Male; D051379:Mice; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000473:pathology*
chemical_list: D000970:Antineoplastic Agents; C497483:CD44 protein, human; D018960:Hyaluronan Receptors