Abstract C6: Barrett's esophagus and esophageal adenocarcinoma: A paradigm for the cancer stem cell model?

Abstract

Abstract Introduction: In recent years, accumulating experimental evidence has suggested that tumors have a hierarchical organisation where only a subset of parenchymal cells, the cancer stem cells (CSCs), has tumor-initiating properties. To date, several antibodies directed against surface antigens have been employed to prospectively isolate CSCs from a broad spectrum of malignancies, though not from esophageal adenocarcinoma. Here, we conducted a series of experiments to test whether Barrett's esophagus and esophageal adenocarcinoma may serve as a disease model for the cancer stem cell concept. Methods: We employed a panel of previously established CSC markers (CD24, CD29, CD44, CD133, CD166, EpCAM) for immunohistochemistry (IHC) analysis and in vivo transplantation assays. Transplantation of serially diluted bulk cancer cells of human tumors into NOD-SCID mice was performed to investigate the presence of CSCs in esophageal adenocarcinoma. Analogous assays were carried out by injecting esophageal cancer cells sorted by FACS using the same panel of CSC markers as employed for IHC analysis. Results: IHC revealed that the intensity of CD24 and CD29 staining tended to increase along the metaplasia — dysplasia — carcinoma sequence. Cells positive for CD24 or CD29 were mainly located in the basal compartment of the metaplastic and dysplastic epithelium. CD44 showed membranous staining mainly in adenocarcinomas, whereas CD166 revealed pronounced cytoplasmic staining in all stages. Serial transplantation experiments with bulk tumor cells indicated that the frequency of tumor-initiating cells in the Lin- population of esophageal adenocarcinoma is approximately 1:50,000 cells. However, to date no tumor growth was observed when tumor cells of subpopulations expressing the above-described CSC markers were transplanted at lower multiplicities. Conclusions: Tumor-initiating cells in esophageal adenocarcinoma are rare, reflecting a hierarchal organisation. However, surface-antigens that have been established as CSC markers in other malignancies do not seem to enrich for tumor initiating cells in esophageal adenocarcinoma. Citation Information: Cancer Res 2009;69(23 Suppl):C6.