Elevated hydrostatic pressure promotes ameloblastoma cell invasion through upregulation of MMP‐2 and MMP‐9 expression via Wnt/β‐catenin signalling

BACKGROUND:The process of marsupialization involves the release of intracystic pressure and the fluid contained within. Marsupialization of cystic ameloblastoma is controversial; therefore, we investigated how hydrostatic pressure influences biological behaviours of ameloblastoma cells and its underlying mechanisms. MATERIALS AND METHODS:An ameloblastoma epithelial cell line, hTERT+ -AM, was exposed to different hydrostatic pressures with or without Dickkopf-related protein 1 (also known as DKK), a canonical Wnt signalling pathway inhibitor. A CCK-8 assay, a monolayer wound assay, and a Transwell assay were used to determine cell proliferation, migration and invasion, respectively. qRT-PCR and Western blot were used to detect expression of MMP-2, MMP-9, RANKL and other downstream targets of Wnt signalling. RESULTS:Elevated hydrostatic pressure promoted migration and invasion of ameloblastoma cells, but inhibited proliferation. Expression of MMP-2, MMP-9, LEF-1, cyclin D1, c-Jun and c-Myc was significantly upregulated under elevated hydrostatic pressure, and these effects could be abolished by DKK1. Expression of RANKL, which is thought to be a downstream target of Wnt signalling, did not significantly change under elevated hydrostatic pressure. CONCLUSIONS:This study indicates that elevated hydrostatic pressure promotes the migration and invasion of ameloblastoma cells by activating the Wnt/β-catenin pathway, thereby increasing expression of MMP-2, MMP-9 and other Wnt signalling downstream targets. This suggests that marsupialization may reduce invasiveness and reverse the bone resorption process by lowering intracystic hydrostatic pressure in cystic ameloblastoma.