Kalampounias Georgios, Varemmenou Athina, Aronis Christos, Mamali Irene, Shaukat Athanasios-Nasir, Chartoumpekis Dionysios V, Katsoris Panagiotis, Michalaki Marina
Division of Genetics, Cell Biology and Development, Department of Biology, School of Natural Sciences, University of Patras, 26504 Patras, Greece.
Endocrine Division, Department of Internal Medicine, School of Medicine, University of Patras, 26504 Patras, Greece.
Cancers (Basel). 2024 Jul 21;16(14):2604. doi: 10.3390/cancers16142604.
Thyrotropin (TSH) suppression is required in the management of patients with papillary thyroid carcinoma (PTC) to improve their outcomes, inevitably causing iatrogenic thyrotoxicosis. Nevertheless, the evidence supporting this practice remains limited and weak, and in vitro studies examining the mitogenic effects of TSH in cancerous cells used supraphysiological doses of bovine TSH, which produced conflicting results. Our study explores, for the first time, the impact of human recombinant thyrotropin (rh-TSH) on human PTC cell lines (K1 and TPC-1) that were transformed to overexpress the thyrotropin receptor (TSHR). The cells were treated with escalating doses of rh-TSH under various conditions, such as the presence or absence of insulin. The expression levels of and () were determined, and subsequently, the proliferation and migration of both transformed and non-transformed cells were assessed. Under the conditions employed, rh-TSH was not adequate to induce either the proliferation or the migration rate of the cells, while expression was increased. Our experiments indicate that clinically relevant concentrations of rh-TSH cannot induce proliferation and migration in PTC cell lines, even after the overexpression of TSHR. Further research is warranted to dissect the underlying molecular mechanisms, and these results could translate into better management of treatment for PTC patients.
在甲状腺乳头状癌(PTC)患者的治疗中,需要进行促甲状腺激素(TSH)抑制以改善其预后,这不可避免地会导致医源性甲状腺毒症。然而,支持这种做法的证据仍然有限且薄弱,并且在体外研究中,检测TSH对癌细胞的促有丝分裂作用时使用的是超生理剂量的牛TSH,结果相互矛盾。我们的研究首次探讨了人重组促甲状腺激素(rh-TSH)对过表达促甲状腺激素受体(TSHR)的人PTC细胞系(K1和TPC-1)的影响。在各种条件下,如有无胰岛素的情况下,用递增剂量的rh-TSH处理细胞。测定了 和 ()的表达水平,随后评估了转化细胞和未转化细胞的增殖和迁移情况。在所采用的条件下,rh-TSH不足以诱导细胞的增殖或迁移率,而 表达增加。我们的实验表明,即使在TSHR过表达后,临床相关浓度的rh-TSH也不能诱导PTC细胞系的增殖和迁移。有必要进一步研究剖析其潜在的分子机制,这些结果可能会转化为对PTC患者更好的治疗管理。