Enhanced basal autophagy supports ameloblastoma-derived cell survival and reactivation

增强的基础自噬支持成釉细胞瘤衍生细胞的存活和再激活

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作者:Rachel C Sharp, Olajumoke A Effiom, Anuradha Dhingra, Onatolu Odukoya, Adetokunbo Olawuyi, Godwin T Arotiba, Kathleen Boesze-Battaglia, Sunday O Akintoye

Conclusions

EP-AMCs exhibit altered autophagic processes that can support survival and recurrence of post-surgical ameloblastoma cells.

Methods

Primary epithelial (EP-AMCs) and mesenchymal (MS-AMCs) ameloblastoma-derived cells were established from tissue samples of solid multicystic ameloblastoma. Clonogenic capacity and basal autophagic capacity were assessed in ameloblastoma-derived cells relative to human odontoma-derived cells (HODCs) and maxilla-mesenchymal stem cells (MX-MSCs). Ability of ameloblastoma-derived cells to survive and form new ameloblastoma was assessed in mouse tumor xenografts.

Results

EP-AMCs were highly clonogenic (p < 0.0001) and demonstrated enhanced basal levels of autophagic proteins microtubule-associated protein 1-light chain 3 (LC3) (p < 0.01), p62 (Sequestosome 1, SQSTM1) (p < 0.01), and the LC3-adapter, melanoregulin (MREG) (p < 0.05) relative to controls. EP-AMCs xenografts regenerated solid ameloblastoma-like tumor with histological features of columnar ameloblast-like cells, loose stellate reticulum-like cells and regions of cystic degeneration characteristic of follicular variant of solid multicystic ameloblastoma. The xenografts also displayed stromal epithelial invaginations strongly reactive to LC3 and p62 suggestive of epithelial-mesenchymal transition and neoplastic odontogenic epithelium. Conclusions: EP-AMCs exhibit altered autophagic processes that can support survival and recurrence of post-surgical ameloblastoma cells.

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