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 β-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. Copyright

Barrett's oesophagus, Cancer stem cells, Oesophageal adenocarcinoma, Tumour-initiating cells
dx.doi.org/10.1002/path.2733, hdl.handle.net/1765/90659
Journal of Pathology
This work was funded by the European Commission 7th Framework Programme; grant id fp7/201662 - An integrated concept of tumor metastasis: implications for therapy (TUMIC)
Department of Surgery

Grotenhuis, B.A, Dinjens, W.N.M, Wijnhoven, B.P.L, Sonneveld, P, Sacchetti, A, Franken, P.F, … Fodde, R. (2010). Barrett's oesophageal adenocarcinoma encompasses tumour-initiating cells that do not express common cancer stem cell markers. Journal of Pathology, 221(4), 379–389. doi:10.1002/path.2733