唾液酸化IgG在肺腺癌中高表达并促进肺腺癌增殖和迁移
Sialylated IgG is highly expressed in lung adenocarcinoma(LUAD)and promotes proliferation and mi-gration of LUAD in mice
葛舒童 1王诗杰 2朱广迎3
作者信息
- 1. 北京大学中日友好临床医学院放射肿瘤科,北京 100029
- 2. 中国医学科学院北京协和医学院,北京 100730
- 3. 北京大学中日友好临床医学院放射肿瘤科,北京 100029;中日友好医院国家呼吸医学中心放射肿瘤科,北京 100029
- 折叠
摘要
目的:探究唾液酸化IgG(SIA-IgG)在肺腺癌(LUAD)中的表达和功能,以及抗SIA-IgG抗体(RP215抗体)对小鼠体内Lewis肺腺癌生长和肿瘤微环境的影响.方法:应用癌症基因组图谱(TCGA)数据库对IgG重链γ恒定区(IGHG)基因进行泛癌分析;用Kaplan-Meier Plotter数据库分析IGHG基因表达与肺腺癌患者预后的关系.克隆形成实验和迁移实验分别评估沉默SIA-IgG后肺腺癌细胞的增殖和迁移能力的变化.采用LLC细胞在雌性C57BU6小鼠(6周龄)体内成瘤并给予RP215抗体治疗,观察小鼠体内肿瘤的生长状况,流式分析观察RP215治疗对肿瘤微环境的影响.结果:泛癌分析,IgG在肺腺癌中表达上调(P＜0.01)且与患者的不良预后呈正相关.小鼠实验,沉默SIA-IgG的表达后,肺腺癌细胞的增殖和迁移能力受到明显抑制(均P＜0.01).RP215抗体治疗可明显抑制小鼠体内Lewis肺腺癌的生长(P＜0.05),且小鼠肿瘤微环境中的巨噬细胞和中性粒细胞比例降低(P＜0.05).结论:SIA-IgG或可作为肺腺癌的潜在治疗靶点.
Abstract
0bjective:To investigate the expression and function of sialylated IgG(SIA-IgG)in LUAD,and the effect of anti-SIA-IgG antibody(RP215 antibody)on the growth and tumor microenvironment of Lewis LUAD in mice.Methods:Pan-cancer analysis of immunoglobulin heavy constant gamma(IGHG)genes was performed using The Cancer Genome Atlas(TCGA)database.The relationship between gene expression of IGHG and sur-vival prognosis of LUAD patients was analyzed using the Kaplan-Meier Plotter database.The expression of SIA-IgG in LUAD PC9 cells was silenced using shRNA,and the knockdown efficiency of SIA-IgG was de-tected by Western blot.Subsequently,clone formation assays and migration assays were utilized to evaluate the proliferation and migration capabilities of LUAD cells.Then,LLC cells were used to form tumors in female C57BL/6 mice(six weeks)and treated with RP215 antibody.The growth of tumors in the mice was observed,and the effect of RP215 treatment on tumor microenvironment was observed by flow cytometry.Results:IgG expression is upregulated in LUAD(P＜0.01)and correlates with poor prognosis.Silencing SIA-IgG expression significantly inhibits the proliferation(P＜0.01)and migration(P＜0.01)capabilities of LUAD cells.Subsequently,treatment with RP215 antibody markedly suppresses Lewis LUAD growth in mice(P＜0.05),and the propor-tion of macrophages and neutrophils in the tumor microenvironment of mice was reduced after RP215 treat-ment(P＜0.05).Conclusion:SIA-IgG may serve as a potential therapeutic target for LUAD.
关键词
肺腺癌/唾液酸化免疫球蛋白G/增殖/迁移Key words
lung adenocarcinoma/sialylated immunoglobulin G/proliferation/migration引用本文复制引用
基金项目
中日友好医院人才引进科研启动基金(2016-RC-4)
出版年
2024
NETL
NSTL
万方数据