Sublethal thermal stress promotes migration and invasion of thyroid cancer cells

Abstract

Objective Radiofrequency ablation is a viable option in the treatment of benign thyroid nodules. Some reports suggest that thermal ablation may also be safe for the management of low-risk thyroid cancer. In this study, we applied transient heat treatment to thyroid cancer cells to mimic clinical scenarios in which insufficient ablation leads to incomplete eradication of thyroid cancer. Methods Differentiated thyroid cancer cell lines B-CPAP, TPC-1, and FTC-133 were subjected to heat treatment at different temperatures for 10 min. Effects on cell growth, clonogenicity, wound healing assay, and Transwell invasion were determined. Results Heat treatment at 45°C or higher reduced cell growth, whereas viability of thyroid cancer cells was not changed after heat treatment at 37, 40, or 42°C. Heat treatment at 40°C increased the number of colony formations by 16% to 39%. Additionally, transient heat treatment at 40°C resulted in a 1.75-fold to 2.56-fold higher migratory activity than treatment at 37°C. Invasive capacity was increased after heat treatment, ranging from 115% to 126%. Expression of several epithelial-mesenchymal transition markers, including ZEB1, N-cadherin, and MMP2, was upregulated following heat treatment at 40°C. Conclusion We for the first time demonstrate that sublethal thermal stress may increase clonogenicity, migration, and invasion of thyroid cancer cells.