Activation of Wnt signalling reduces the population of cancer stem cells in ameloblastoma

Hyun Yi Kim, Shujin Li, Dong Joon Lee, Jin Hoo Park, Takashi Muramatsu, Hidemitsu Harada, Young Soo Jung, Han Sung Jung

Research output: Contribution to journalArticlepeer-review

Abstract

Objectives: The treatment of ameloblastoma, an odontogenic epithelial tumour destroying jawbone, mainly depends on radical destructive resections. Other therapeutic options are limited by the characteristics of ameloblastoma, such as high recurrence rates and resistance to radiation and chemotherapy, which implies possible existence of cancer stem cells (CSCs) in ameloblastoma. Here, we identified a putative CSC population in immortalized and primary human ameloblastoma cells and examined possible therapeutic reagents to reduce the CSC population. Methods: We investigated subpopulations of AM-1 cell line and human ameloblastoma cells using immunocytochemistry and flow cytometry and the effects of Wnt signalling activators on the 2- and 3-dimensional cultured ameloblastoma cells using molecular biological analyses. Result: Among heterogenous ameloblastoma cells, small-sized and round-shaped cells were found to be proliferative and expressed a marker of dental epithelial stem cells, SRY-box 2 (Sox2). Exogenous activation of Wnt signalling using glycogen synthase kinase 3β inhibitors, lithium chloride (LiCl) and valproic acid (VPA), increased the cell size and decreased proliferation of cells and expression of Sox2 in 2 dimensionally cultured AM-1 and human primary ameloblastoma cells. Furthermore, the growth of 3 dimensionally cultured AM-1 cells as suspended or embedded in gel was suppressed by treatment with Wnt signalling activators, VPA and CHIR99021, or antibodies to sclerostin, an antagonist of Wnt signalling. Conclusion: We suggest that Wnt signalling activators are potential drug candidates to suppress CSCs in ameloblastoma.

Original languageEnglish
Article numbere13073
JournalCell Proliferation
Volume54
Issue number7
DOIs
Publication statusPublished - 2021 Jul

Bibliographical note

Funding Information:
This work was supported by the National Research Foundation of Korea (NRF) Grant funded by the Korea Government (MSIP) (NRF‐2019R1A2C3005294, NRF2017M3A9B3061833). ‐

Funding Information:
This work was supported by the National Research Foundation of Korea (NRF) Grant funded by the Korea Government (MSIP) (NRF-2019R1A2C3005294, NRF-2017M3A9B3061833).

Publisher Copyright:
© 2021 The Authors. Cell Proliferation Published by John Wiley & Sons Ltd.

All Science Journal Classification (ASJC) codes

  • Cell Biology

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