Different expression pattern of stem cell markers in xenografts of human biliary tract cancer cell lines

Aims: Tumour cells have the capability to trans- and to de-differentiate by re-expressing embryonic development genes and stem cell characteristics. The aim of this study was to investigate the expression of putative markers of stem- and progenitor cells in vivo and in vitro using a xenograft model of different human biliary tract cancer (BTC) cell lines.Materials and Methods: Human BTC cell lines CCLP-1, Egi-1, MzChA-1, MzChA-2, SkChA-1, TFK-1 and GBC were cultured under standard conditions in vitro and implanted subcutaneously (5×10⁶ cells) in male NMRI mice. Xenograft tissue specimens were characterized for proliferation (cell cycle proteins) and markers of differentiation (intermediate filaments) as well as of stem- and progenitor cells (BMI-1, Sox-2, Nestin, CD133, CD44 and Nanog) by RT-PCR and immunohistochemistry. Results: The investigated BTC cell lines showed a low to moderate and partially significant different expression pattern of the stem cell markers in following descending order: CD133 >> CD44 and Nanog >> BMI-1, Sox-2 and Nestin. These stem cell markers were associated with each other as well with morphological and molecular markers of proliferation and differentiation on mRNA and protein level. Additionally, hierarchical cluster analysis classified the BTC xenografts in subgroups with homogenous expression of stem cell markers. Conclusion: The analysis of expression patterns of putative stem cell markers in a xenograft model classified the human BTC into subgroups possibly indicating and reflecting the heterogeneity of carcinogenesis in BTC. Additionally, prognostic relevance of the findings must be proven in further experimental and morphological studies of human tumour specimens of BTC.

biliary tract cancer - stem cell markers - xenograft