The interplay between the epithelial permeability barrier, cell migration and mitochondrial metabolism of growth factors and their inhibitors in a human endometrial carcinoma cell line.

IF 3.6 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Tissue Barriers Pub Date : 2024-10-01 Epub Date: 2024-01-15 DOI:10.1080/21688370.2024.2304443
Takumi Konno, Takayuki Kohno, Shin Kikuchi, Arisa Kura, Kimihito Saito, Tadahi Okada, Hiroshi Shimada, Yuya Yamazaki, Tomoki Sugiyama, Motoki Matsuura, Yuki Ohsaki, Tsuyoshi Saito, Takashi Kojima
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Abstract

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.

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人子宫内膜癌细胞系的上皮通透性屏障、细胞迁移和生长因子及其抑制剂的线粒体代谢之间的相互作用。
众所周知,人类子宫内膜异位症和子宫内膜癌的紧密连接功能、细胞迁移和线粒体代谢存在异常。在这项研究中,我们研究了生长因子及其抑制剂对人类子宫内膜异位症子宫内膜癌泽野细胞 2D 和 2.5D 培养上皮通透性屏障、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以及纤毛的生成。生长因子 TGF-β 和 EGF 影响了泽野细胞 2D 和 2.5D 培养液的上皮通透性屏障、细胞迁移以及双细胞和三细胞紧密连接分子的表达。EW-7197(一种 TGF-β 受体抑制剂)、AG1478(一种表皮生长因子受体抑制剂)和 SP600125(一种 JNK 抑制剂)影响了上皮通透性屏障、细胞迁移和线粒体代谢,并阻止了 TGF-β 和 EGF 在 2D 和 2.5D 培养物中诱导的变化。EW-7197 和 AG1478 可诱导 2.5D 培养物中的纤毛生成。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之间的相互作用促进子宫内膜癌的恶性发展。EW-7197和AG1478可作为子宫内膜癌的新型治疗方案。
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来源期刊
Tissue Barriers
Tissue Barriers MEDICINE, RESEARCH & EXPERIMENTAL-
CiteScore
6.60
自引率
6.50%
发文量
25
期刊介绍: Tissue Barriers is the first international interdisciplinary journal that focuses on the architecture, biological roles and regulation of tissue barriers and intercellular junctions. We publish high quality peer-reviewed articles that cover a wide range of topics including structure and functions of the diverse and complex tissue barriers that occur across tissue and cell types, including the molecular composition and dynamics of polarized cell junctions and cell-cell interactions during normal homeostasis, injury and disease state. Tissue barrier formation in regenerative medicine and restoration of tissue and organ function is also of interest. Tissue Barriers publishes several categories of articles including: Original Research Papers, Short Communications, Technical Papers, Reviews, Perspectives and Commentaries, Hypothesis and Meeting Reports. Reviews and Perspectives/Commentaries will typically be invited. We also anticipate to publish special issues that are devoted to rapidly developing or controversial areas of research. Suggestions for topics are welcome. Tissue Barriers objectives: Promote interdisciplinary awareness and collaboration between researchers working with epithelial, epidermal and endothelial barriers and to build a broad and cohesive worldwide community of scientists interesting in this exciting field. Comprehend the enormous complexity of tissue barriers and map cross-talks and interactions between their different cellular and non-cellular components. Highlight the roles of tissue barrier dysfunctions in human diseases. Promote understanding and strategies for restoration of tissue barrier formation and function in regenerative medicine. Accelerate a search for pharmacological enhancers of tissue barriers as potential therapeutic agents. Understand and optimize drug delivery across epithelial and endothelial barriers.
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