微囊藻毒素-LR处理的中性粒细胞NETs促进结直肠癌细胞迁移

doi:10.16352/j.issn.1001-6325.2023.06.0967

基础医学与临床 ›› 2023, Vol. 43 ›› Issue (6): 967-973.doi: 10.16352/j.issn.1001-6325.2023.06.0967

微囊藻毒素-LR处理的中性粒细胞NETs促进结直肠癌细胞迁移

张海灵^1,2, 杨玉², 周倩倩², 汪远金², 王婷^1*

1.南京医科大学基础医学院细胞生物学系,江苏南京 211166;
2.安徽医科大学临床医学院,安徽合肥 230031

收稿日期:2023-01-05 修回日期:2023-03-25 出版日期:2023-06-05 发布日期:2023-05-31
通讯作者: ^*wangting@njmu.edu.cn
基金资助:
安徽省高等学校省级生物化学课程思政示范课程(2021kcszsfkc215);安徽医科大学临床医学院校级科研项目(2021XJ020)

Neutrophil NETs treated with microcystin-LR promote migration of colorectal cancer cell

ZHANG Hailing^1,2, YANG Yu², ZHOU Qianqian², WANG Yuanjin², WANG Ting^1*

1. Department of Cell Biology, School of Basic Medicine, Nanjing Medical University, Nanjing 211166;
2. Clinical Medical College of Anhui Medical University, Hefei 230031, China

Received:2023-01-05 Revised:2023-03-25 Online:2023-06-05 Published:2023-05-31
Contact: ^*wangting@njmu.edu.cn

摘要/Abstract

摘要： 目的探究微囊藻毒素-LR(MC-LR)处理的中性粒细胞外诱捕网(NETs)对结直肠癌细胞迁移的影响。方法同位素标记相对和绝对定量(iTRAQ)技术检测经MC-LR处理的结直肠癌细胞培养上清中蛋白质的表达,GO功能富集分析差异表达的蛋白富集的生物学过程。流式细胞测量术检测MC-LR灌胃后的裸鼠皮下异种移植肿瘤组织中中性粒细胞的数量;免疫组化实验检测经MC-LR处理的BALB/c小鼠原位癌组织中CD11b,中性粒细胞弹性蛋白酶(NE)和瓜氨酸组蛋白3(citH3)的表达;Transwell小室法检测经MC-LR处理之后的NETs对结直肠癌细胞迁移的影响。结果 MC-LR处理之后筛选出11个差异表达的蛋白(P＜0.05),并发现与白细胞迁移过程有关的差异蛋白发生了富集;MC-LR能够增加裸鼠皮下肿瘤组织中中性粒细胞的数量(P＜0.05);灌胃MC-LR的BALB/c小鼠原位结直肠癌组织中CD11b,NE和citH3的表达较对照组增多(P＜0.05);MC-LR处理后的NETs能够增强结直肠癌细胞的迁移能力(P＜0.05)。结论 MC-LR可能通过诱导肿瘤微环境(TME)中NETs的形成进而促进结直肠癌细胞的迁移。

关键词: 微囊藻毒素-LR, 结直肠癌, 中性粒细胞外诱捕网, 迁移, 肿瘤微环境

Abstract: Objective To investigate whether neutrophils extracellular traps (NETs) treated with microcystin-LR may promote the migration of colorectal cancer cell. Methods Isobaric tags for relative and absolute quantification (iTRAQ) technology was used to detect the secreted proteins in colorectal cancer cell culture supernatant after MC-LR exposure, and Gene Ontology (GO) functional enrichment analysis was performed to analyze in which pathway the differentially expressed proteins were enriched. The quantity of neutrophils in MC-LR-treated tumor tissue of xenograft nude mice was detected by flow cytometry. The expressions of CD11b, neutrophil elastase (NE) and citrulline histones 3 (citH3) in colorectal cancer tissues of BALB/c mice treated with MC-LR were detected by immunohistochemistry. The effect of NETs treated with MC-LR on colorectal cancer cell migration was determined by Transwell migration assay. Results Eleven differentially expressed proteins treated with MC-LR were screened out after MC-LR exposure(P＜0.05), and the differentially expressed proteins were enriched in the way of leukocyte migration. MC-LR increased the counting of neutrophils in colorectal cancer tissue of nude mice (P＜0.05). The expression of CD11b, NE and citH3 in orthotopic colorectal cancer tissues of BALB/c mice was increased after MC-LR administration compared with those in control group (P＜0.05). NETs treated with MC-LR enhanced the migration of colorectal cancer cell (P＜0.05). Conclusions MC-LR may promote migration of colorectal cancer cell by inducing the formation of NETs in the tumor microenvironment (TME).

Key words: microcystin-LR, colorectal cancer, neutrophil extracellular traps, migration, tumor microenvironment

中图分类号:

张海灵, 杨玉, 周倩倩, 汪远金, 王婷. 微囊藻毒素-LR处理的中性粒细胞NETs促进结直肠癌细胞迁移[J]. 基础医学与临床, 2023, 43(6): 967-973.

ZHANG Hailing, YANG Yu, ZHOU Qianqian, WANG Yuanjin, WANG Ting. Neutrophil NETs treated with microcystin-LR promote migration of colorectal cancer cell[J]. Basic & Clinical Medicine, 2023, 43(6): 967-973.

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微囊藻毒素-LR处理的中性粒细胞NETs促进结直肠癌细胞迁移

Neutrophil NETs treated with microcystin-LR promote migration of colorectal cancer cell

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