Identification of tumor stem-like cells in admanatimomatous craniopharyngioma and determination of these cells' pathological significance.

Abstract

Nuclear β-catenin, a hallmark of active canonical Wnt signaling, can be histologically detected in a subset of cells and cell clusters in up to 94% of adamantinomatous craniopharyngioma (ACP) samples. However, it is unclear whether nuclear β-catenin-containing cells within human ACPs possess the characteristics of tumor stem cells, and it is unknown what role these cells have in ACP. Primary ACP cells were cultured from 12 human ACP samples. Adamantinomatous CP stem cell-like cells (CSLCs) showing CD44 positivity were isolated from the cultured primary ACP cells by performing magnetic-activated cell sorting. The tumor sphere formation, cell cycle distribution, stemness marker expression, and multidifferentiation potential of the CD44- cells and the CSLCs were analyzed. Compared with the CD44- cells, the cultured human CSLCs formed tumor spheres and expressed CD44 and CD133; moreover, these cells demonstrated nuclear translocation of β-catenin. In addition, the CSLCs demonstrated osteogenic and adipogenic differentiation capacities compared with the CD44- cells. The CSLCs also displayed the capacity for tumor initiation in human-mouse xenografts. These results indicate that CSLCs play an important role in ACP development, calcification, and cystic degeneration.