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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 
 CELL PROLIFERATION, Vol.54(7) : e13073, 2021-07 
Journal Title
Issue Date
Ameloblastoma / metabolism ; Ameloblastoma / pathology ; Animals ; Cell Culture Techniques ; Cell Line, Tumor ; Cell Proliferation / drug effects ; Cell Size / drug effects ; Down-Regulation / drug effects ; Humans ; Lithium Chloride / pharmacology* ; Mice ; Mice, Nude ; Neoplastic Stem Cells / cytology ; Neoplastic Stem Cells / metabolism* ; SOXB1 Transcription Factors / metabolism ; Valproic Acid / pharmacology ; Wnt Signaling Pathway / drug effects* ; beta Catenin / metabolism
Wnt signalling ; ameloblastoma ; cancer stem cell
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.
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Appears in Collections:
2. College of Dentistry (치과대학) > Dept. of Oral Biology (구강생물학교실) > 1. Journal Papers
2. College of Dentistry (치과대학) > Dept. of Oral and Maxillofacial Surgery (구강악안면외과학교실) > 1. Journal Papers
Yonsei Authors
Park, Jin Hoo(박진후) ORCID logo https://orcid.org/0000-0003-2337-9554
Jung, Young Soo(정영수) ORCID logo https://orcid.org/0000-0001-5831-6508
Jung, Han Sung(정한성) ORCID logo https://orcid.org/0000-0003-2795-531X
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