title: Prediction of response to radiotherapy in the treatment of esophageal cancer using stem cell markers.
abstract: OBJECTIVE
  In this study, we investigated whether cancer stem cell marker expressing cells can be identified that predict for the response of esophageal cancer (EC) to CRT.
  
  
  METHODS
  EC cell-lines OE-33 and OE-21 were used to assess in vitro, stem cell activity, proliferative capacity and radiation response. Xenograft tumors were generated using NOD/SCID mice to assess in vivo proliferative capacity and tumor hypoxia. Archival and fresh EC biopsy tissue was used to confirm our in vitro and in vivo results.
  
  
  RESULTS
  We showed that the CD44+/CD24- subpopulation of EC cells exerts a higher proliferation rate and sphere forming potential and is more radioresistant in vitro, when compared to unselected or CD44+/CD24+ cells. Moreover, CD44+/CD24- cells formed xenograft tumors faster and were often located in hypoxic tumor areas. In a study of archival pre-neoadjuvant CRT biopsy material from EC adenocarcinoma patients (N=27), this population could only be identified in 50% (9/18) of reduced-responders to neoadjuvant CRT, but never (0/9) in the complete responders (P=0.009).
  
  
  CONCLUSIONS
  These results warrant further investigation into the possible clinical benefit of CD44+/CD24- as a predictive marker in EC patients for the response to chemoradiation.
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Surgery, Section of Surgical Oncology, The Netherlands.
authors.forename: Justin K
authors.initials: JK
authors.lastname: Smit
authors.forename: Hette
authors.initials: H
authors.lastname: Faber
authors.forename: Maarten
authors.initials: M
authors.lastname: Niemantsverdriet
authors.forename: Mirjam
authors.initials: M
authors.lastname: Baanstra
authors.forename: Johan
authors.initials: J
authors.lastname: Bussink
authors.forename: Harry
authors.initials: H
authors.lastname: Hollema
authors.forename: Ronald P
authors.initials: RP
authors.lastname: van Os
authors.forename: John Th M
authors.initials: JT
authors.lastname: Plukker
authors.forename: Robert P
authors.initials: RP
authors.lastname: Coppes
mesh_terms: D000230:Adenocarcinoma / Q000737:chemistry / Q000473:pathology / Q000628:therapy*; D000818:Animals; D015415:Biomarkers; D051927:CD24 Antigen / Q000032:analysis*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D059248:Chemoradiotherapy; D004938:Esophageal Neoplasms / Q000737:chemistry / Q000473:pathology / Q000628:therapy*; D006801:Humans; D018960:Hyaluronan Receptors / Q000032:analysis*; D051379:Mice; D016513:Mice, SCID; D014411:Neoplastic Stem Cells / Q000473:pathology*
chemical_list: D015415:Biomarkers; D051927:CD24 Antigen; C497483:CD44 protein, human; D018960:Hyaluronan Receptors
keywords: Cancer stem cells; Chemoradiotherapy; Esophageal cancer; Radiotherapy; Response