首页|巨噬细胞迁移抑制因子在垂体神经内分泌肿瘤的表达及促肿瘤发生和发展机制的研究

巨噬细胞迁移抑制因子在垂体神经内分泌肿瘤的表达及促肿瘤发生和发展机制的研究

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目的 探讨巨噬细胞迁移抑制因子(MIF)在垂体腺瘤(PAs)中的表达及对肿瘤发生发展的作用及其机制.方法 纳入2021年11月至2022年7月在华中科技大学同济医学院附属同济医院神经外科收治的PAs患者20例.收集患者的手术标本.检测肿瘤组织及PAs细胞系(GH3、AtT20和TtT/GF)MIF分子的转录和表达水平.采用慢病毒转染构建稳定转染的MIF过表达(oeMIF)和沉默(shMIF)的细胞系.采用划痕实验、体外组织肿瘤种植模型、酶联免疫吸附试验(ELISA)实验等检测MIF表达改变对细胞迁移、促肾上腺皮质激素(ACTH)激素分泌、组织肿瘤侵袭和血管生成的影响.两组间比较采用两样本独立t检验.结果 PAs患者的MIF表达水平明显高于对照组(2.850±0.838比1.065±0.435,t=3.565,P<0.01).MIF在PAs细胞系中表达高于对照组(GH3:1.730±0.260 比 1.001±0.091,t=5.957,P<0.01;AtT20:1.853±0.108 比 1.008±0.147,t=8.307,P<0.01;TtT/GF:3.087±0.21 比 1.008±0.147,t=15.430,P<0.01).oeMIF 的PAs细胞系划痕迁移愈合率高于对照组(0.758±0.044比0.581±0.045,t=4.903,P<0.01),而shMIF的PAs细胞系划痕迁移愈合率低于对照组(0.425±0.036比0.581±0.045,t=4.689,P<0.01).shMIF组肿瘤血管生成的分叉点及分支数均明显少于对照组(分叉点:53.652±15.675比35.304±10.218,t=4.703,P<0.01;分支数:35.913±6.721 比 30.609±6.854,t=2.650,P<0.05).oeMIF 的 PAs 细胞系分泌 ACTH 水平高于对照组(1.198±0.026 比 1.000±0.077,t=4.863,P<0.01),而shMIF的PAs细胞系分泌ACTH水平低于对照组(0.845±0.034比1.000±0.077,t=3.673,P<0.05).结论 垂体瘤组织和细胞系MIF表达增加,MIF可能产生促进PAs发生发展及ACTH分泌的作用.
Expression of macrophage migration inhibitory factor in pituitary neuroendocrine tumors and the mechanism of promoting tumor occurrence and development
Objective To detect the expression of macrophage migration inhibitory factor(MIF)in pituitary adenomas(PAs)and its role and mechanism in tumor development.Methods Totally,20 pa-tients with PAs were enrolled in the Department of Neurosurgery,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology from November 2021 to July 2022.The surgical specimens were collected from patients.The transcription and expression levels of MIF were detected in tumor tissues and pituitary adenoma cell lines(GH3,AtT20 and TtT/GF).Lentiviral transfection was used to construct stably transfected MIF overexpressing(oeMIF)and silenced(shMIF)cell lines.Scratch experiments,in vitro tissue tumor implantation models,and enzyme linked immunosorbent assay(ELISA)experiments were used to detect the effects of changes in MIF expression on cell migration,adrenocorticotropic hormone(ACTH)hormone secretion,tissue tumor invasion,and angiogenesis.Two-sample independent t-test was used to compare the two groups.Results The expression of MIF was significantly increased in patients with PAs(2.850±0.838 vs.1.065±0.435,t=3.565,P<0.01).The expression of MIF was increased in pituitary adenoma cell lines(GH3:1.730±0.260 vs.1.001±0.091,t=5.957,P<0.01;AtT20:1.853±0.108 vs.1.008±0.147,t=8.307,P<0.01;TtT/GF:3.087±0.21 vs.1.008±0.147,t=15.430,P<0.01).The scratch healing rate of pituitary adenoma cell line of oeMIF was higher than that of the control group(0.758±0.044 vs.0.581±0.045,t=4.903,P<0.01),while that of shMIF pitui-tary adenoma cell line was lower than that of the control group(0.425±0.036 vs.0.581±0.045,t=4.689,P<0.01).The number of junctions and branches of tumor angiogenesis in the shMIF group were significantly less than those in the control group(junctions:53.652±15.675 vs.35.304±10.218,t=4.703,P<0.01;branches:35.913±6.721 vs.30.609±6.854,t=2.650,P<0.05).The level of ACTH secreted by pituitary adenoma cell line of oeMIF was higher than that of control group(1.198±0.026 vs.1.000±0.077,t=4.863,P<0.01)while the level of ACTH secreted by pituitary adenoma cell lines of shMIF was lower than that of the control group(0.845±0.034 vs.1.000±0.077,t=3.673,P<0.05).Conclusion The expression of MIF increases in pituitary tumor tissues and cell lines,and MIF may promote the occurrence and development of PAs and the secretion of ACTH.

Pituitary adenomasMacrophage migration inhibitory factorMigrationAdreno-corticotropic hormone

王光辉、陈娟、向志高、刘京典、朱洪涛、吴思思、王晶、舒凯、雷霆

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华中科技大学同济医学院附属同济医院神经外科,武汉 430030

垂体腺瘤 巨噬细胞迁移抑制因子 迁移 促肾上腺皮质激素

2024

中华实验外科杂志
中华医学会

中华实验外科杂志

CSTPCD
影响因子:0.759
ISSN:1001-9030
年,卷(期):2024.41(9)