TGF-β对膀胱癌组织中巨噬细胞来源肿瘤相关成纤维细胞的影响及其机制  

Effect and mechanism of TGF-βon macrophage-derived cancer-associated fibroblasts in bladder can-cer tissue

作　　者：蒲石 沈成全 胡鼎 赵新钊 秦瑞泽 刘昌学 王永华[1,2] PU Shi;SHEN Chengquan;HU Ding;ZHAO Xinzhao;QIN Ruize;LIU Changxue;WANG Yonghua(Department of Urology,The Affiliated Hospital of Qingdao University,Qingdao 266003,China)

机构地区：[1]青岛大学附属医院泌尿外科,山东青岛266003 [2]青岛市泌尿系统疾病临床医学研究中心

出　　处：《精准医学杂志》2024年第3期203-208,共6页Journal of Precision Medicine

基　　金：国家自然科学基金项目(81772713)。

摘　　要：目的探讨TGF-β对膀胱癌组织中巨噬细胞来源肿瘤相关成纤维细胞(CAF)的影响及其机制。方法采用Kaplan-Meier法分析膀胱癌组织中α-SMA^(+)CD68^(+)CAF表达水平与患者的总生存率(OS)的关系;采用免疫荧光技术检测α-SMA^(+)CD68^(+)CAF在膀胱癌组织中的浸润情况;采用Western blot实验检测TGF-β对α-SMA^(+)CD68^(+)CAF体外诱导作用。同时构建膀胱癌小鼠模型,采用免疫荧光技术和免疫组化法检测TGF-β对膀胱癌小鼠体内α-SMA^(+)CD68^(+)CAF的诱导作用及对CD8^(+)T细胞浸润的影响。结果膀胱癌组织中α-SMA与CD68的表达呈正相关,且α-SMA^(+)CD68^(+)CAF高表达的患者预后更差(χ^(2)=9.05,P<0.05)。免疫荧光技术检测结果显示,膀胱癌组织中存在α-SMA^(+)CD68^(+)CAF。Western blot实验检测结果显示,TGF-β可显著促进α-SMA^(+)CD68^(+)CAF的生成。膀胱癌小鼠模型体内实验显示,TGF-β可促进膀胱癌组织中α-SMA^(+)CD68^(+)CAF的生成,从而抑制CD8^(+)T细胞的浸润。结论TGF-β可显著促进膀胱癌组织中巨噬细胞来源CAF的生成,从而抑制CD8^(+)T细胞的浸润。Objective To investigate the effect and mechanism of TGF-βon macrophage-derived cancer-associated fibroblasts(CAFs)in bladder cancer tissue.Methods The Kaplan-Meier method was used to investigate the relationship between the expression ofα-SMA^(+)CD68^(+)CAF and overall survival(OS)in bladder cancer;immunofluorescence assay was used to observe the infiltration ofα-SMA^(+)CD68^(+)CAF in bladder cancer tissue;Western blot was used to observe the inductive effect of TGF-βonα-SMA^(+)CD68^(+)CAF in vitro.A mouse model of bladder cancer was established,and immunofluorescence assay and immunohistochemistry were used to observe the inductive effect of TGF-βonα-SMA^(+)CD68^(+)CAF and its effect on the infiltration of CD8^(+)T cells in mice with bladder cancer.Results The expression ofα-SMA was positively correlated with that of CD 68 in bladder can-cer tissue,and the patients with a high expression level ofα-SMA^(+)CD68^(+)CAF tended to have a poorer prognosis(χ^(2)=9.05,P<0.05).Immunofluorescence assay showed the presence ofα-SMA^(+)CD68^(+)CAF in bladder cancer tissue,and Western blot showed that TGF-βcould significantly promote the production ofα-SMA^(+)CD68^(+)CAF.In vivo experiments in a mouse model of bladder cancer showed that TGF-βpromoted the generation ofα-SMA^(+)CD68^(+)CAF in bladder cancer tissue,thereby inhibiting the infiltration of CD8^(+)T cells.Conclusion TGF-βcan significantly promote the production of macrophage-derived CAF in bladder cancer tissue,thereby inhibiting the infiltration of CD8^(+)T cells.

关 键 词：转化生长因子β 癌相关成纤维细胞 膀胱肿瘤 肿瘤相关巨噬细胞 免疫耐受 CD8阳性T淋巴细胞 细胞浸润 

分 类 号：R737.14[医药卫生—肿瘤]