Inhibition of Metalloproteinases-2, -9, and -14 Suppresses Papillary Thyroid Carcinoma Cell Migration and Invasion

Papillary thyroid carcinoma (PTC), while often having a favorable prognosis, can progress to aggressive forms. Matrix metalloproteinases (MMPs) are crucial in extracellular matrix remodeling and are implicated in tumor invasion and metastasis. This study investigated MMP expression and activity in PTC and the efficacy of two selective MMP inhibitors in suppressing PTC cell migration and invasion. The analysis of RNA-seq data from the TCGA-THCA dataset highlighted the overexpression of MMP-14 in PTC, a key upstream activator of several MMPs, including MMP-2 and, indirectly, MMP-9. This elevation correlated with disease status and recurrence risk. Validation in a cell model, using PTC lines (K1 and BCPAP) and non-tumoral thyroid cells (Nthy-ori 3-1), showed markedly increased MMP-14 activity in PTC lines (6-fold in K1; 11-fold in BCPAP). MMP-9 activity was also substantially elevated (386-fold in K1; 131-fold in BCPAP), along with increased MMP-2 activity. We then tested selective inhibitors. NSC405020, an MMP-14 inhibitor, reduced K1 cell migration by 56.52% and invasion by 67.3%. Gallic acid, an MMP-2 and MMP-9 inhibitor, reduced K1 cell migration to 60.3% and invasion to 33.3% relative to the controls. These findings suggest that elevated MMP activity is a hallmark of aggressive PTC, underscoring MMPs' role in cancer progression. Targeting MMPs, particularly with agents like NSC405020 and gallic acid, presents a promising therapeutic strategy to disrupt PTC tumor progression.