Adamiok-Ostrowska Anna, Grzanka Małgorzata, Czarnocka Barbara
Department of Biochemistry and Molecular Biology, Centre of Postgraduate Medical Education, 01-813 Warsaw, Poland.
Oncol Lett. 2023 Sep 25;26(5):483. doi: 10.3892/ol.2023.14070. eCollection 2023 Nov.
Agrin (AGRN) is a matricellular glycoprotein involved in extracellular signal transduction. AGRN is involved in tumorigenesis and cancer progression; however, the role of AGRN in thyroid cancer (TC) remains unclear. In the present study, using cell lines derived from various subtypes of TC including CGTH, FTC-133 and BcPAP and transcriptomic data from patients with TC, the role of AGRN in TC was analyzed by migration, invasion, viability and proliferation assays as well as Western blot with EMT markers. AGRN expression was significantly increased in thyroid tumors and cell lines derived from various TC subtypes. The highest AGRN expression was found in follicular and papillary thyroid carcinoma subtypes. Immunocytochemistry revealed nuclear AGRN localization in normal (NTHY) and TC cells. Silencing of AGRN decreased viability, proliferation, migration and invasion of TC cell lines by upregulating vimentin and downregulating N-cadherin and E-cadherin. Furthermore, the expression of AGRN was associated with neutrophil infiltration in thyroid tumors. In conclusion, the present results indicated that increased AGRN expression promoted tumorigenic phenotypes of TC cells, while AGRN expression was associated with immune infiltration in thyroid tumors. AGRN may represent a target for future cancer therapy and requires further evaluation.
聚集蛋白(AGRN)是一种参与细胞外信号转导的基质细胞糖蛋白。AGRN参与肿瘤发生和癌症进展;然而,AGRN在甲状腺癌(TC)中的作用仍不清楚。在本研究中,使用源自TC各种亚型(包括CGTH、FTC - 133和BcPAP)的细胞系以及TC患者的转录组数据,通过迁移、侵袭、活力和增殖测定以及使用上皮 - 间质转化(EMT)标志物的蛋白质免疫印迹分析了AGRN在TC中的作用。AGRN表达在甲状腺肿瘤和源自各种TC亚型的细胞系中显著增加。在滤泡状和乳头状甲状腺癌亚型中发现AGRN表达最高。免疫细胞化学显示正常(NTHY)和TC细胞中AGRN定位于细胞核。沉默AGRN通过上调波形蛋白并下调N - 钙黏蛋白和E - 钙黏蛋白来降低TC细胞系的活力、增殖、迁移和侵袭。此外,AGRN的表达与甲状腺肿瘤中的中性粒细胞浸润有关。总之,目前的结果表明,AGRN表达增加促进了TC细胞的致瘤表型,而AGRN表达与甲状腺肿瘤中的免疫浸润有关。AGRN可能代表未来癌症治疗的一个靶点,需要进一步评估。