101P Establishing novel chordoma cell systems: Functional characterization of brachyury dynamics and stemness pathways

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Background: Papillary thyroid carcinoma (PTC) often has a favorable prognosis but can progress to aggressive forms.Matrix metalloproteinases (MMPs), especially MMP-2, MMP-9, and MMP-14, are key in ECM remodeling and linked to tumor invasion and metastasis.Our study examined MMP expression/activity in PTC and the potential of gallic acid (GA) and NSC405020 to inhibit MMP activity, thereby suppressing PTC cell migration and invasion.Methods: We analyzed MMP activity in PTC cell lines (K1, BCPAP) versus normal thyroid cells (Nthy-ori 3-1).K1 cells were treated with GA or NSC405020 for 24 hours.Cell migration and invasion were assessed by chamber migration and Matrigel invasion assays.MMP activity (MMP-2, MMP-9) was determined by gelatin zymography, and MMP-14 activity via fluorimetric assay.Cell viability was measured by MTT or Crystal Violet.Data are mean ± SEM from ≥3 independent experiments; significance by unpaired t-tests.Results: PTC cell lines showed significantly increased MMP activity versus normal cells: MMP14 up to 11-fold, gelatinases MMP2/MMP9 up to 386-fold.Specifically, K1 cells had 6-fold higher MMP14 (p<0.001),386-fold higher MMP9 (p=0.003), and 1.9-fold higher MMP2 (p=0.048)activity.NSC405020 significantly inhibited K1 cell migration and invasion without affecting viability.50 μM NSC405020 reduced migration by 76.67% (p=0.006).12.5 μM NSC405020 reduced migration by 38.33% (p=0.034) and invasion by 67.3% (p=0.0055).Gallic Acid (GA) reduced K1 cell migration and invasion, and inhibited MMP2/MMP9 activity without cytotoxicity.50 μM GA reduced MMP9 activity by 25.7% (p=0.0026) and MMP2 activity by 41.9% (p=0.0018).For migration, 50 μM GA caused a 35.7% reduction (p=0.037), and 75 μM GA a 60.3% reduction (p=0.022).50 μM GA reduced invasion by 33.3% (p=0.032).Conclusions: MMPs, especially MMP-2, MMP-9, and MMP-14, are highly active in PTC cells.Both gallic acid and NSC405020 effectively inhibit PTC cell invasion and migration, suggesting their promise as targeted therapeutic agents to counteract PTC progression.These compounds warrant further research for novel therapeutic strategies.

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