Department of Cell Science, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.
Department of Anatomy, Sapporo Medical University School of Medicine, Sapporo, Japan.
Tissue Barriers. 2024 Oct;12(4):2304443. doi: 10.1080/21688370.2024.2304443. Epub 2024 Jan 15.
It is known that there are abnormalities of tight junction functions, cell migration and mitochondrial metabolism in human endometriosis and endometrial carcinoma. In this study, we investigated the effects of growth factors and their inhibitors on the epithelial permeability barrier, cell migration and mitochondrial metabolism in 2D and 2.5D cultures of human endometrioid endometrial carcinoma Sawano cells. We also investigated the changes of bicellular and tricellular tight junction molecules and ciliogenesis induced by these inhibitors. The growth factors TGF-β and EGF affected the epithelial permeability barrier, cell migration and expression of bicellular and tricellular tight junction molecules in 2D and 2.5D cultures of Sawano cells. EW-7197 (a TGF-β receptor inhibitor), AG1478 (an EGFR inhibitor) and SP600125 (a JNK inhibitor) affected the epithelial permeability barrier, cell migration and mitochondrial metabolism and prevented the changes induced by TGF-β and EGF in 2D and 2.5D cultures. EW-7197 and AG1478 induced ciliogenesis in 2.5D cultures. In conclusion, TGF-β and EGF promoted the malignancy of endometrial cancer via interplay among the epithelial permeability barrier, cell migration and mitochondrial metabolism. EW-7197 and AG1478 may be useful as novel therapeutic treatments options for endometrial cancer.
已知在人类子宫内膜异位症和子宫内膜癌中存在紧密连接功能、细胞迁移和线粒体代谢的异常。在这项研究中，我们研究了生长因子及其抑制剂对人子宫内膜样腺癌 Sawano 细胞二维和 2.5 维培养物中上皮通透性屏障、细胞迁移和线粒体代谢的影响。我们还研究了这些抑制剂诱导的双细胞和三细胞紧密连接分子的变化和纤毛发生。生长因子 TGF-β 和 EGF 影响 Sawano 细胞二维和 2.5 维培养物中的上皮通透性屏障、细胞迁移和双细胞和三细胞紧密连接分子的表达。EW-7197（TGF-β 受体抑制剂）、AG1478（EGFR 抑制剂）和 SP600125（JNK 抑制剂）影响上皮通透性屏障、细胞迁移和线粒体代谢，并阻止 TGF-β 和 EGF 在二维和 2.5 维培养物中诱导的变化。EW-7197 和 AG1478 诱导 2.5 维培养物中的纤毛发生。总之，TGF-β 和 EGF 通过上皮通透性屏障、细胞迁移和线粒体代谢的相互作用促进了子宫内膜癌的恶性转化。EW-7197 和 AG1478 可能是子宫内膜癌的新治疗选择。
