Adenosine triphosphate regulates metastatic behaviors of oral squamous cell carcinoma cells

This study aimed to investigate the effects of extracellular adenosine triphosphate (eATP) on the migration and extracellular matrix (ECM) homeostasis of oral squamous cell carcinoma (OSCC) cells. Two tongue-origin OSCC cell lines, HSC-4 (metastatic) and HSC-7 (primary), were treated with various concentrations of eATP (0-200 µM). Cell viability and migration were assessed using MTT and scratch assays. The mRNA expression of matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) was analyzed by RT-qPCR. MMP9 and MMP3 release was detected by ELISA. P₂Y₁ and P₂Y₂ involvement was assessed using MRS2179 and AR-C118925, respectively. Both cell lines expressed numerous P₂ receptors. 50 µM eATP selectively downregulated MMP8 and MMP9 expression in both lines and reduced MMP9 and MMP3 secretion, whereas TIMP levels remained unchanged. P₂Y₁ inhibition reversed eATP-mediated MMP suppression, whereas P₂Y₂ inhibition suppressed MMP expression. eATP influenced cell proliferation in both cell lines at different time points. 200 µM eATP reduced migration and increased E-cadherin expression in HSC-4, whereas no migratory changes were observed in HSC-7. eATP modulates OSCC migration and ECM homeostasis. These findings indicate that eATP-purinergic signaling plays a pivotal role in ECM dynamics in OSCC and is a potential target for effective treatment of tongue-origin OSCC.