首页|NUSAP1在肿瘤相关巨噬细胞中的表达及对非小细胞肺癌的影响

NUSAP1在肿瘤相关巨噬细胞中的表达及对非小细胞肺癌的影响

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目的 探究NUSAP1 在肿瘤相关巨噬细胞中表达对非小细胞肺癌的影响机制.方法 使用Western blot检测检测人癌和癌周巨噬细胞中NUSAP1、p-PI3K以及MMP-9 的相对蛋白表达量;使用慢病毒感染M2 巨噬细胞,构建骨髓诱导M2 与人非小细胞肺癌细胞株Lewis 共培养体外模拟NSCLC肿瘤微环境,使用Western blot检测M2巨噬细胞中NUSAP1、p-PI3K以及MMP-9的相对蛋白表达量.使用细胞划痕实验检测非小细胞肺癌细胞的迁移能力.结果 人体样本Western blot检测结果显示非小细胞肺癌组织中NUSAP1,PI3K与MMP-9 的相对蛋白表达量显著高于癌周组织(P<0.05);体外实验通过小鼠巨噬细胞与Lewis 共培养以模拟体内肿瘤环境,Western blot检测慢病转染敲低NUSAP1 后p-PI3K与MMP-9 均表达降低(P<0.05),上调NUSAP1 后p-PI3K与MMP-9 表达均升高(P<0.05).MMP-9过表达(OV-MMP-9)抵消了由于敲低NUSAP1 所造成的MMP-9表达水平降低,同时shRNA-NUSAP1+ ovMMP-9组侵袭率明显高于shRNA-NUSAP1+OVNC组(P<0.05).shRNANUSAP1(NUSAP1 敲低)组比shNUSAP1 组的迁移宽度明显增加,说明迁移能力受限;在敲低NUSAP1 的基础尚过表达MMP-9(OV-MMP-9)后迁移能力明显变强,迁移宽度显著变小(P<0.05).结论 NUSAP1 在肿瘤相关巨噬细胞中通过促进PI3K通路的激活及MMP-9 的表达从而促进非小细胞肺癌细胞的迁移.
Influence of the expression level of NUSAP1 in tumor-associated macrophages on non-small cell lung cancer
Objective To investigate the effect of the expression level of nucleolar and spindle-associated protein 1(NUSAP1)in tumor-associated macrophages on non-small cell lung cancer(NSCLC).Methods Protein expressions of NUSAP1,p-Phosphatidylinositol 3-kinase(PI3K),and matrix metallopeptidase 9(MMP-9)macrophages of NSCLC and paracancerous tissues were detected by Western blot.M2 macrophages were infected with lentiviruses to construct a bone marrow-induced M2 co-culture system with the NSCLC cell line Lewis,thus simulating the tumor microenvironment in vitro.Western blot was used to detect the relative protein expressions of NUSAP1,p-PI3K,and MMP-9 in M2 macrophages.The migration ability of NSCLC cells was tested using a cell scratch assay.Results Western blot results showed that the protein expressions of NUSAP1,PI3K,and MMP-9 were significantly upregulated in NSCLC tissues than those of paracancerous tissues(P<0.05).In the in vitro tumor microenvironment of bone marrow-induced M2 co-culture system with Lewis cells,knockdown of NUSAP1 significantly downregulated p-PI3K and MMP-9,which were significantly upregulated by overexpressing NUSAP1(P<0.05).Transfection of OV-MMP-9 to overexpress it reversed the downregulated MMP-9 by knockdown of NUSAP1.The invasive rate was significantly higher in cells transfected with shRNA-NUSAP1+OV-MMP-9 than those transfected with shRNA-NUSAP1+OVNC(P<0.05).Transfection of shRNA-NUSAP1 significantly increased the width of scratching,suggesting the inhibited migration.Co-transfection of sh-NUSAP1+OV-MMP-9 significantly decreased the width of scratching,suggesting the enhanced migration ability(P<0.05).Conclusion NUSAP1 promotes the migration ability of NSCLC cells by promoting the activation of the PI3K pathway and the expression of MMP-9 in tumor-associated macrophages.

non-small cell lung cancer(NSCLC)nucleolar and spindle-associated protein 1(NUSAP1)tumor-associated macrophagesphosphatidylinositol 3-kinase(PI3K)matrix metallopeptidase 9(MMP-9)

李晓敏、于哲、曹珊珊、槐梅、韩洪涌

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062552 河北省任丘市,华北石油管理局总医院病理科

062552 河北省任丘市,华北石油管理局总医院普胸科

062552 河北省任丘市,华北石油管理局总医院体检中心

山东省平度市中心医院心胸科

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非小细胞肺癌(NSCLC) NUSAP1 肿瘤相关巨噬细胞 PI3K MMP-9

河北省卫生健康委员会项目

20190114

2024

10.3969/j.issn.1002-7386.2024.02.009

河北医药
河北省医学情报研究所

河北医药

CSTPCD
影响因子：1.075
ISSN：1002-7386
年,卷(期)：2024.46(2)
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