Exposure to environmental pollutants is suspected to be one of the potential causes accounting for the increase in thyroid cancer (TC) incidence worldwide. Among the ubiquitous pollutants, per-polyfluoroalkyl substances (PFASs), were demonstrated to exert thyroid disrupting effects. Perfluoroalkyl carboxylates (PFCAs) represent a subgroup of PFAS and include perfluoro carboxylic acids (PFOA and PFHxA) and perfluoropolyether carboxylic acid (C6O4). Two models of normal thyroid cells in primary cultures: Adherent (A-NHT) and Spheroids (S-NHT) were employed. A-NHT and S-NHT were exposed to C6O4, PFOA or PFHxA (0; 0.01; 0.1, 1; 10; 100; 1000 ng/mL) to assess viability (WST-1 and AV/PI assay), evaluate spherification index (SI) and volume specifically in S-NHT. CXCL8 and CCL2 (mRNA and protein), and EMT-related genes were assessed in both models after exposure to PFCAs. PFHxA reduced the viability of both A-NHT and S-NHT. None of the PFCAs interfered with the volume or spherification process in S-NHT. CXCL8 and CCL2 mRNA and protein levels were differently up-regulated by each PFCAs, being PFOA and PFHxA the stronger inducers. Moreover, among the tested PFCAs, PFHxA induced a more consistent increase in the mRNA levels of EMT-related genes. : This is the first evaluation of the effects of exposure to PFCAs on factors potentially involved in establishing the TC microenvironment. PFHxA modulated the TC microenvironment at three levels: cell viability, pro-tumorigenic chemokines, and EMT-genes. The results provide further evidence of the pro-tumorigenic effect of PFOA. On the other hand, a marginal effect was observed for C6O4 on pro-tumorigenic chemokines.

中文翻译：

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PFCA 是否驱动甲状腺癌微环境的建立？ C6O4、PFOA 和 PFHxA 暴露对两种原代培养人甲状腺细胞模型的影响


接触环境污染物被怀疑是全球甲状腺癌（TC）发病率增加的潜在原因之一。在普遍存在的污染物中，全多氟烷基物质（PFAS）被证明会产生甲状腺干扰作用。全氟烷基羧酸盐 (PFCA) 是 PFAS 的一个亚类，包括全氟羧酸（PFOA 和 PFHxA）和全氟聚醚羧酸 (C6O4)。采用原代培养物中正常甲状腺细胞的两种模型：贴壁细胞（A-NHT）和球体细胞（S-NHT）。将 A-NHT 和 S-NHT 暴露于 C6O4、PFOA 或 PFHxA（0; 0.01; 0.1, 1; 10; 100; 1000 ng/mL）以评估活力（WST-1 和 AV/PI 测定），评估球化指数(SI) 和体积，特别是 S-NHT。在暴露于 PFCA 后，对两个模型中的 CXCL8 和 CCL2（mRNA 和蛋白质）以及 EMT 相关基因进行了评估。 PFHxA 降低了 A-NHT 和 S-NHT 的活力。所有 PFCA 均不会干扰 S-NHT 中的体积或球化过程。每种 PFCA 不同程度地上调 CXCL8 和 CCL2 mRNA 和蛋白质水平，其中 PFOA 和 PFHxA 是更强的诱导剂。此外，在测试的 PFCA 中，PFHxA 诱导 EMT 相关基因的 mRNA 水平更加一致地增加。 ：这是首次评估接触 PFCA 对可能涉及建立 TC 微环境的因素的影响。 PFHxA 在三个层面上调节 TC 微环境：细胞活力、促肿瘤趋化因子和 EMT 基因。结果进一步证明了 PFOA 的促肿瘤作用。另一方面，观察到 C6O4 对促肿瘤趋化因子的边际效应。