Study on the promotion of invasiveness of pituitary adenoma cells by activating EMT through S100A4

doi:10.3969/j.issn.1000-1565.2025.04.007

Abstract

Abstract: S100A4 protein is a calcium binding protein involved in angiogenesis, cell differentiation, apoptosis, and autophagy processes. In order to study the expression of S100A4 in pituitary adenomas and further explore its mechanism in promoting the invasive nature of pituitary adenoma cells, the expression of S100A4 in invasive and non-invasive pituitary adenoma tissues was detected through immunohistochemical techniques. A pituitary adenoma cell line with stable overexpression of S100A4 was obtained by transfection technology. Scratch assay and Transwell assay were employed to respectively detect the changes in cell migration and invasion capabilities. RT-PCR and Western blot methods were used- DOI:10.3969/j.issn.1000-1565.2025.04.007S100A4启动EMT促进垂体腺瘤细胞的侵袭性研究赵鹏飞,王佳良,王岩,白泽通,孙程圆,刘超,刘海鹏(河北大学附属医院神经外科,河北保定 071000)摘要:S100A4 蛋白是一种钙结合蛋白,参与血管生成、细胞分化、细胞凋亡和自噬过程.为了研究S100A4在垂体腺瘤中的表达情况,并进一步探索其在促进垂体腺瘤细胞侵袭性中的作用机制,通过免疫组化技术检测S100A4在侵袭性垂体腺瘤组织和非侵袭性垂体腺瘤组织中的表达情况,采用转染技术获得稳定过表达S100A4的垂体腺瘤细胞系,采用划痕实验和Transwell实验分别检测细胞的迁移和侵袭能力的变化,采用RT-PCR和Western blot法检测细胞中EMT标志物的表达情况,通过免疫组化技术检测EMT标志物在非侵袭性及侵袭性垂体腺瘤组织中的表达情况.结果显示:在侵袭性垂体腺瘤组织中,S100A4高表达,E-cadherin低表达,N-cadherin和Vimentin高表达,而在非侵袭性垂体腺瘤组织中分子表达情况相反;过表达S100A4可显著促进垂体腺瘤细胞的迁移和侵袭能力,过表达S100A4可显著下调垂体腺瘤细胞中E-cadherin的mRNA和蛋白表达水平,显著上调N-cadherin、Vimentin的mRNA和蛋白表达水平.综上,S100A4在垂体腺瘤细胞中的过表达可通过促进EMT进程,提高细胞迁移和侵袭的能力,表明S100A4可能是治疗垂体腺瘤侵袭性生长的新靶点.关键词:S100A4;垂体腺瘤;EMT;迁移;侵袭中图分类号:R739.4 文献标志码:A 文章编号:1000-1565(2025)04-0389-09Study on the promotion of invasiveness of pituitary adenoma cells by activating EMT through S100A4ZHAO Pengfei,WANG Jialiang,WANG Yan,BAI Zetong,SUN Chengyuan,LIU Chao,LIU Haipeng(Department of Neurosurgery, Affiliated Hospital of Hebei University, Baoding 071000,China)Abstract: S100A4 protein is a calcium binding protein involved in angiogenesis, cell differentiation, apoptosis, and autophagy processes. In order to study the expression of S100A4 in pituitary adenomas and further explore its mechanism in promoting the invasive nature of pituitary adenoma cells, the expression of S100A4 in invasive and non-invasive pituitary adenoma tissues was detected through immunohistochemical techniques. A pituitary adenoma cell line with stable overexpression of S100A4 was obtained by transfection technology. Scratch assay and Transwell assay were employed to respectively detect the changes in cell migration and invasion capabilities. RT-PCR and Western blot methods were used- 收稿日期:2024-10-28;修回日期:2024-12-26 基金项目:河北省医学科学研究课题计划项目(20220625;20220626);河北大学附属医院基金项目(2022QC79;2022QC56) 第一作者:赵鹏飞(1989—),男,河北大学附属医院主治医师,主要从事中枢神经系统肿瘤的临床和基础研究.E-mail:zpf03539@126.com 通信作者:刘海鹏(1980—),男,河北大学附属医院副主任医师,主要从事中枢神经系统肿瘤的临床和基础研究.E-mail:lhp01116@163.com 第4期赵鹏飞等:S100A4启动EMT促进垂体腺瘤细胞的侵袭性研究河北大学学报(自然科学版) 第45卷to detect the expression of EMT markers in cells. The expression of EMT markers in non-invasive and invasive pituitary adenoma tissues was examined by immunohistochemical techniques. The results indicated that in invasive pituitary adenoma tissues, S100A4 was highly expressed, E-cadherin was lowly expressed, and N-cadherin and Vimentin were highly expressed. In non-invasive pituitary adenoma tissues, the molecular expressions were the opposite. Overexpression of S100A4 significantly promoted the migration and invasion abilities of pituitary adenoma cells. Overexpression of S100A4 significantly downregulated the mRNA and protein expression levels of E-cadherin in pituitary adenoma cells and significantly upregulated the mRNA and protein expression levels of N-cadherin and Vimentin. In conclusion, the overexpression of S100A4 in pituitary adenoma cells can enhance migration and invasion ability by promoting the EMT process, suggesting that S100A4 may be a new target for treating aggressive growth of pituitary adenoma.

Key words: S100A4, pituitary adenoma, EMT, migration, invasion

CLC Number:

R739.4

ZHAO Pengfei,WANG Jialiang,WANG Yan,BAI Zetong,SUN Chengyuan,LIU Chao,LIU Haipeng. Study on the promotion of invasiveness of pituitary adenoma cells by activating EMT through S100A4[J]. Journal of Hebei University(Natural Science Edition), 2025, 45(4): 389-397.

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