癌相关成纤维细胞源性SULF1对非小细胞肺癌细胞生物学行为的影响和机制  

The effects and mechanisms of cancer-associated fibroblast-derived SULF1 on the biological behavior of non-small cell lung cancer

作　　者：汤正波 沈玉光 舒德军 TANG Zhengbo;SHEN Yuguang;SHU Dejun(Department of Thoracic Surgery,Zunyi First People's Hospital(the Third Affiliated Hospital of Zunyi Medical University),Guizhou Zunyi 563000,China)

机构地区：[1]遵义市第一人民医院(遵义医科大学第三附属医院)胸外科,贵州遵义563000

出　　处：《现代肿瘤医学》2023年第21期3933-3938,共6页Journal of Modern Oncology

基　　金：贵州省遵义市科技局科技计划项目[编号:遵市科合HZ字(2021)272号]。

摘　　要：目的:探讨癌相关成纤维细胞(cancer-associated fibroblasts,CAFs)衍生的硫酸酯酶1(sulfatase1,SULF1)对非小细胞肺癌(non-small cell lung cancer,NSCLC)进展的影响。方法:从癌旁组织和NSCLC组织中分离正常成纤维细胞(normal fibroblasts,NFs)和CAFs,将NFs-CM和CAFs-CM与NSCLC细胞共培养。干预CAFs中SULF1的表达。CCK8检测细胞增殖,Transwell检测侵袭,Western Blot检测上皮间质转化(epithelial-mesenchymal transition,EMT)相关蛋白(E-cadherin、N-cadherin)和Wnt/β-catenin通路核心蛋白(Wnt3、β-catenin)的表达。构建裸鼠成瘤模型,评估CAFs分泌的SULF1对肿瘤生长的影响。结果:与NFs-CM相比,CAFs-CM促进NSCLC细胞增殖、侵袭和EMT(P<0.01)。与CAFs^(si-NC)-CM组相比,CAFs^(si-SULF1)-CM组细胞增殖、侵袭和EMT被抑制(P<0.01)。与CAFs^(vector)-CM组比较,过表达SULF1能够上调Wnt3和β-catenin的表达(P<0.001)。但是CAFs中SULF1过表达对NSCLC细胞的影响被Wnt/β-catenin通路抑制剂部分挽救。体内研究显示,CAFs促进肿瘤生长和Ki67表达,而敲低SULF1则抑制肿瘤生长以及瘤组织中Ki67表达。结论:CAFs来源的SULF1通过激活Wnt/β-catenin通路诱导NSCLC的进展。Objective:To explore the effects of sulfatase1(SULF1)derived from cancer-associated fibroblasts(CAFs)on the progression of non-small cell lung cancer(NSCLC).Methods:Normal fibroblasts(NFs)and CAFs were isolated from paracancer tissue and NSCLC tissue,NFs-CM and CAFs-CM were co-cultured with NSCLC cells.SULF1 expression in CAFs was intervented.Cell proliferation was detected by CCK8,invasion was detected by Transwell,and epithelial-mesenchymal transition(EMT)-related proteins(E-cadherin,N-cadherin)and core proteins of Wnt/β-catenin pathway(Wnt3,β-catenin)were detected by Western Blot.The tumor formation model of nude mice was established to evaluate the effects of SULF1 secreted by CAFs on tumor growth.Results:Compared with NFs-CM,CAFs-CM promoted proliferation,invasion and EMT of NSCLC cells(P<0.01).Compared with CAFs^(si-NC)-CM group,cell proliferation,invasion and EMT were inhibited in CAFs^(si-SULF1)-CM group(P<0.01).Compared with CAFs^(vector)-CM group,overexpression of SULF1 could up-regulate the expression of Wnt3 andβ-catenin(P<0.001).However,the effects of SULF1 overexpression in CAFs on NSCLC cells was partially saved by Wnt/β-catenin pathway inhibitors.In vivo studies showed that CAFs promote tumor growth and Ki67 expression,while SULF1 knockdown inhibits tumor growth and Ki67 expression in tumor tissues.Conclusion:CAFs-derived SULF1 induces NSCLC progression by activating the Wnt/β-catenin pathway.

关 键 词：癌症相关成纤维细胞 硫酸酯酶1 WNT/Β-CATENIN通路 非小细胞肺癌 

分 类 号：R734.2[医药卫生—肿瘤]