Keywords
tight junctions
metastasis
thyroid carcinomas
How to Cite
Abstract
Epithelial-mesenchymal transition (EMT) has a decisive influence on the process of metastasis (Mts) formation. A key event of EMT is the reorganization of tight junctions (TJs). The TJ membrane is based on scaffold, adapter and signaling proteins, which include ZO-1-3 (zonula occludens) proteins. ZO proteins play an important role in inflammation, tumorigenesis, cancer progression, etc., affecting cell proliferation and motility and are considered tumor suppressors. It has been repeatedly proven that ZO proteins are diffused or lost in almost all types of inflammation, during tumor formation and Mts. The aim was to compare the amount of ZO-1 in the tissues and blood of patients with papillary thyroid carcinoma (PTC) without Mts and
with Mts to the lymph nodes. Material and methods. Postoperative samples of tumor tissue, Mts and conditionally normal tissue were used for the studies. Blood was obtained by standard venipuncture and stored in EDTA tubes at -80 ºС. The amount of ZO-1 was determined using E-EL-H1516 enzyme immunoassay kits (Elabscience, USА). The study involved patients with PTC and goiter. Group 1 included patients with PTC without Mts, group 2 – with PTC and Mts, group 3 – with goiter. Results. The obtained data indicate that the level of ZO-1 in the conditionally normal thyroid tissue is 2 times higher than in tumor tissue of PTC without Mts. In PTC with Mts, the amount of ZO-1 is significantly lower than in the conditionally normal thyroid tissue, both with and without Mts. In goiter tissue, the amount of ZO-1 does not differ from that in conditionally normal carcinoma tissue, but is significantly higher than in tumor tissue and Mts. The level of ZO-1 in the blood of PTC patients is significantly lower than in the blood of healthy people. The amount of ZO-1 in the blood of PTC patients with Mts is lower and significantly different from that of patients with PTC without Mts. Сonclusions. Thus, a decrease in ZO-1 concentration in tumors and blood may be one of the markers of Mts in PTC.
References
Yang J, Antin P, Berx G, Blanpain C, Brabletz T, Bronner M, et al. Guidelines and definitions for research on epithelial-mesenchymal transition. Nat Rev Mol Cel Biol. 2020 Jun;21(6):341-352. doi:10.1038/s41580-020-0237-9.
Citi S, Fromm M, Furuse M, González-Mariscal L, Nusrat A, Tsukita S, et al. A short guide to the tight junction. J Cell Sci. 2024 May 1;137(9):jcs261776. doi:10.1242/jcs.261776.
Saito AC, Endo C, Fukazawa Y, Higashi T, Chiba H. Effects of TAMP family on the tight junction strand network and barrier function in epithelial cells. Ann N Y Acad Sci. 2022 Nov;1517(1):234-250. doi:10.1111/nyas.14889.
Cording J, Berg J, Käding N, Bellmann C, Tscheik C, Westphal JK, et al. In tight junctions, claudins regulate the interactions between occludin, tricellulin and marvelD3, which, inversely, modulate claudin oligomerization. J Cell Sci. 2013 Jan 15;126(Pt 2):554-64. doi:10.1242/jcs.114306.
Rouaud F, Sluysmans S, Flinois A, Shah J, Vasileva E, Citi S. Scaffolding proteins of vertebrate apical junctions: structure, functions and biophysics. Biochim Biophys Acta Biomembr. 2020 Oct 1;1862(10):183399. doi:10.1016/j.bbamem.2020.183399.
Wibbe N, Ebnet K. Cell adhesion at the tight junctions: new aspects and new functions. Cells. 2023 Nov 24;12(23):2701. doi:10.3390/cells12232701.
Otani T, Furuse M. Tight junction structure and function revisited. Trends Cell Biol. 2020 Oct;30(10):815-817. doi:10.1016/j. tcb.2020.08.004.
Zhang S, Xu W, Wang H, Cao M, Li M, Zhao J, et al. Inhibition of CREB-mediated ZO-1 and activation of NF-kappaB-induced IL-6 by colonic epithelial MCT4 destroys intestinal barrier function. Cell Prolif. 2019 Nov;52(6):e12673. doi: 10.1111/cpr.12673.
Yu S, He J, Xie K. Zonula occludens proteins signaling in inflammation and tumorigenesis. Int J Biol Sci. 2023 Jul 24;19(12):3804-3815. doi:10.7150/ijbs.85765.
Chang ZY, Liu HM, Leu YL, Hsu CH, Lee TY. Modulation of gut microbiota combined with upregulation of intestinal tight junction explains anti-inflammatory effect of corylin on colitisassociated cancer in mice. Int J Mol Sci. 2022 Feb 28;23(5):2667. doi: 10.3390/ijms23052667.