AlMuzaini, Anwar A A Y
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PublicationThe Interplay of Hypoxia and Autophagy in Epithelial-Derived Ameloblastoma Cell Survival: A Pilot Study(2020-05-18) AlMuzaini, Anwar A A YAmeloblastoma is the most clinically-significant benign odontogenic jaw tumor with a locally-aggressive growth pattern and high malignant transformation rate. Epithelial-derived ameloblastoma cells (EPAMCs) demonstrate enhanced basal autophagy but the etiopathogenesis of ameloblastoma and the roles of hypoxia and autophagy in EPAMCs survival and recurrence are still unknown. The goals of this study were to assess expression of ameloblastoma-specific markers and the roles of hypoxia and autophagy on EPAMC survival. Primary and recurrent ameloblastoma tissues from two patients were immunostained with pan-cytokeratin, vimentin and SQSTM1/p62. Additionally, EPAMCs were subjected to severe hypoxia (0.1% O2) to define responsiveness to hypoxia based on expression of hypoxic and autophagic markers. Human odontoma-derived cells (HODCs) served as control. Both primary and recurrent tissue samples stained positive for pan-cytokeratin. Vimentin and SQSTM1/p62 were undetectable but the connective tissue stained positive for vimentin. Phosphorylated-40S ribosomal protein S6 (pS6) levels were decreased in EPAMC in both hypoxia and post-hypoxia. There were no significant changes among the remainder markers or between the EPAMC and HODCs. While the small sample size of this pilot study limited the statistical power several interesting trends were observed. In EPAMCs, canonical autophagy tended to be active at baseline, hypoxia, and re-oxygenation but did not increase when cells were subjected to hypoxia. Cells displayed reduced levels of pS6 and elevated levels of LC3ABII/LC3ABI and p62 24 hours following hypoxia. The vimentin expression and pan-cytokeratin pattern are consistent with an epithelial origin of ameloblastoma. Our data also suggests EPAMCs are using autophagy to survive severe hypoxia.