title: Barrett's oesophageal adenocarcinoma encompasses tumour-initiating cells that do not express common cancer stem cell markers.
abstract: Accumulating evidence has suggested that tumours have a hierarchical organization in which only the cancer stem cells (CSCs) have tumour-initiating properties. Several surface antigens have been employed to isolate CSCs from various malignancies, although not from oesophageal adenocarcinoma (EA). We tested whether Barrett's oesophagus (BE) and EA might serve as a model for the CSC concept. In vivo assays were performed by transplantation of serially diluted bulk EA cells into NOD-SCID mice to establish the presence and frequency of tumour-initiating cells. These were found to be present as ca. 1 in 64 000 cells. The transplanted tumours fully recapitulated the primary lesions. Subsequently, a panel of previously established CSC markers was employed for immunohistochemistry. CD24, CD29 and CD44 showed heterogeneous staining in EA. Nuclear beta-catenin accumulation increased during progression from metaplasia to dysplasia and was often observed in the basal compartment with CD24 and CD29 staining. However, the overall staining patterns were not such to clearly point out specific candidate markers. Accordingly, all markers were employed to sort the corresponding subpopulations of cancer cells and transplant them at low multiplicities in NOD-SCID mice. No increased tumour-initiating capacity of sorted EA cells was observed upon transplantation. These results indicate that tumour-initiating cells are present in EA, thus reflecting a hierarchical organization. However, antibodies directed against novel surface antigens are needed to detect subpopulations enriched for CSCs in EA by transplantation assays.
authors.affiliation: Department of Surgery, Josephine Nefkens Institute, Erasmus Medical Centre, Rotterdam, The Netherlands.
authors.forename: Brechtje A
authors.initials: BA
authors.lastname: Grotenhuis
authors.forename: Winand N M
authors.initials: WN
authors.lastname: Dinjens
authors.forename: Bas P L
authors.initials: BP
authors.lastname: Wijnhoven
authors.forename: Petra
authors.initials: P
authors.lastname: Sonneveld
authors.forename: Andrea
authors.initials: A
authors.lastname: Sacchetti
authors.forename: Patrick F
authors.initials: PF
authors.lastname: Franken
authors.forename: Herman
authors.initials: H
authors.lastname: van Dekken
authors.forename: Hugo W
authors.initials: HW
authors.lastname: Tilanus
authors.forename: J Jan B
authors.initials: JJ
authors.lastname: van Lanschot
authors.forename: Riccardo
authors.initials: R
authors.lastname: Fodde
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D001471:Barrett Esophagus / Q000378:metabolism / Q000473:pathology*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002471:Cell Transformation, Neoplastic / Q000378:metabolism / Q000473:pathology; D018450:Disease Progression; D004938:Esophageal Neoplasms / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D011230:Precancerous Conditions / Q000378:metabolism / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor