title: Clinical and biological significance of stem-like CD133(+)CXCR4(+) cells in esophageal squamous cell carcinoma.
abstract: OBJECTIVE
  Esophageal squamous cell carcinoma is one of the most frequent malignant tumors. Cancer stem cells are considered to be responsible for tumor growth, metastasis, and recurrence. Cluster of differentiation 133 (CD133) and C-X-C chemokine receptor type 4 (CXCR4) are frequently applied markers for the identification and isolation of cancer stem cells. However, few studies have investigated the coexpression of CD133 and CXCR4 in esophageal squamous cell carcinoma. This study aims to explore the clinical and biological role of stem-like CD133(+)CXCR4(+) cells in esophageal squamous cell carcinoma.
  
  
  METHODS
  Immunohistochemical staining was performed to detect the expression of CD133 and CXCR4 in esophageal squamous cell carcinoma tissues of patients. Flow cytometry and fluorescence-activated cell sorting were applied to analyze and isolate each subgroup in esophageal squamous cell carcinoma cell line TE-1. The characteristic differences between each subgroup were assayed in vitro. The association between CD133/CXCR4 expression and patients' prognosis was analyzed by Kaplan-Meier and Cox regression.
  
  
  RESULTS
  Among 154 patient tissues, concomitant high CD133-CXCR4 expression accounts for 20.78% (32/154). In vitro, CXCR4(+) cells (CD133(+)CXCR4(+) and CD133(-)CXCR4(+)) showed high invasive potential and CD133(+)CXCR4(+) cells showed high proliferative capacity. Clinically, patients with concomitant high CD133-CXCR4 expression had decreased disease-free survival and overall survival (P < .01).
  
  
  CONCLUSIONS
  Esophageal squamous cell carcinoma cells coexpressing CD133 and CXCR4 possess the characteristics of cancer stem cells. The concomitant high CD133-CXCR4 expression might be a novel marker for predicting the poor prognosis of patients with esophageal squamous cell carcinoma, and CD133 and CXCR4 may serve as potential therapeutic targets.
authors.affiliation: Department of Thoracic Surgery, The Affiliated Zhongshan Hospital of Fudan University, Shanghai, People's Republic of China.
authors.forename: Chunlai
authors.initials: C
authors.lastname: Lu
authors.affiliation: Department of Thoracic Surgery, The Affiliated Zhongshan Hospital of Fudan University, Shanghai, People's Republic of China.
authors.forename: Fengkai
authors.initials: F
authors.lastname: Xu
authors.affiliation: Department of Thoracic Surgery, The Affiliated Zhongshan Hospital of Fudan University, Shanghai, People's Republic of China.
authors.forename: Jie
authors.initials: J
authors.lastname: Gu
authors.affiliation: Department of Thoracic Surgery, The Affiliated Zhongshan Hospital of Fudan University, Shanghai, People's Republic of China.
authors.forename: Yunfeng
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Department of Thoracic Surgery, The Affiliated Zhongshan Hospital of Fudan University, Shanghai, People's Republic of China.
authors.forename: Guangyin
authors.initials: G
authors.lastname: Zhao
authors.affiliation: Department of Nephrology, The Affiliated Zhongshan Hospital of Fudan University, Shanghai, People's Republic of China.
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Yu
authors.affiliation: Department of Thoracic Surgery, The Affiliated Zhongshan Hospital of Fudan University, Shanghai, People's Republic of China. Electronic address: gedi6902@hotmail.com.
authors.forename: Di
authors.initials: D
authors.lastname: Ge
mesh_terms: D000071916:AC133 Antigen; D015703:Antigens, CD / Q000032:analysis*; D014408:Biomarkers, Tumor / Q000032:analysis*; D002294:Carcinoma, Squamous Cell / Q000276:immunology* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002469:Cell Separation / Q000379:methods; D018572:Disease-Free Survival; D004938:Esophageal Neoplasms / Q000276:immunology* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D005434:Flow Cytometry; D006023:Glycoproteins / Q000032:analysis*; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D014411:Neoplastic Stem Cells / Q000276:immunology* / Q000473:pathology; D010455:Peptides / Q000032:analysis*; D016016:Proportional Hazards Models; D019718:Receptors, CXCR4 / Q000032:analysis*
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D014408:Biomarkers, Tumor; C527276:CXCR4 protein, human; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; D019718:Receptors, CXCR4
keywords: CD133; CXCR4; cancer stem-like cells; esophageal squamous cell carcinoma