Thyroid cancer risk associated with perfluoroalkyl carboxylate exposure: Assessment using a human dermal fibroblast–derived extracellular matrix–based thyroid cancer organoid

The burgeoning incidence of thyroid cancer globally necessitates a deeper understanding of its etiological factors. Emerging research suggests a link to environmental contaminants, notably perfluoroalkyl carboxylates (PFACs). This study introduces a novel biomaterial-based approach for modeling thyroid cancer and assesses PFAC exposure-related health risks. This biomaterial-centric methodology enabled a realistic simulation of long-term, low-dose PFAC exposure, yielding critical insights into their carcinogenic potential. Initially, the no observed adverse effect level concentration of 10 μM for four different PFACs, determined using cytotoxicity tests in 2D cell cultures, was employed with thyroid cancer organoids. Specifically, these organoids were exposed to 10 μM of PFACs, refreshed every 3 days over a period of 21 days. The impact of these PFACs on the organoids was assessed using western blotting and immunofluorescence, complemented by high-content screening imaging. This evaluation focused on thyroid-specific biomarkers, epithelial-mesenchymal transition markers, and the proliferation marker Ki-67. Findings indicated significant alterations in these markers, particularly with long-chain PFACs, suggesting an increased risk of thyroid cancer progression and metastasis upon prolonged exposure. This research advances our understanding of thyroid cancer pathology within the context of environmental health risks by investigating the effects of low-dose, long-term exposure to PFACs on human thyroid cancer organoids. The findings reveal the potential carcinogenic risk associated with these substances, emphasizing the urgent need for stricter regulatory controls.