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

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OBJECTIVE

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.

METHODS

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.

RESULTS

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.

CONCLUSIONS

These results indicate that CSLCs play an important role in ACP development, calcification, and cystic degeneration.

ABBREVIATIONS ACP = adamantinomatous craniopharyngioma; bFGF = basic fibroblast growth factor; CP = craniopharyngioma; CSLC = CP stem cell–like cell; DMEM = Dulbecco’s modified Eagle’s medium; EDTA = ethylenediaminetetraacetic acid; EGF = epidermal growth factor; ExoSAP = exonuclease I and shrimp alkaline phosphatase; FBS = fetal bovine serum; GAPDH = glyceraldehyde 3-phosphate dehydrogenase; HEPES = 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid; MACS = magnetic-activated cell sorting; Pan-CK = pan-cytokeratin; PBS = phosphate-buffered saline; PVDF = polyvinylidene difluoride; qPCR = quantitative polymerase chain reaction; SDS-PAGE = sodium dodecyl sulfate–polyacrylamide gel electrophoresis.

Supplementary Materials

  • Supplemental Tables 1-3 (PDF 476 KB)
Article Information

Contributor Notes

Correspondence Yi Liu: Nanfang Hospital, Southern Medical University, Guangzhou, China. liuyi86818@126.com.INCLUDE WHEN CITING Published online August 30, 2019; DOI: 10.3171/2019.5.JNS19565.

C.H.W., S.T.Q., J.F., J.P., and J.X.P. contributed equally to this study.

Disclosures This work is supported by grants from the Science and Technology Program of Guangdong (2016A020213006, 2017A020215048, and 2017A020215191); the Natural Science Foundation of Guangdong (2016A030310377); the Science and Technology Program of Guangzhou (201707010149); and the President Foundation of Nanfang Hospital, Southern Medical University (2015C018, 2016L002, and 2017Z009).

© AANS, except where prohibited by US copyright law.

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