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肿瘤微环境中M2巨噬细胞调控CLDN10通路促进膀胱癌细胞的上皮-间质转化
M2 macrophages promotes bladder cancer EMT through CLDN10 involved signaling pathway in tumor micro-environment
- 第三军医大学学报 2021年43卷第23期 页码：2525-2531
- 作者机构：
1.400030 重庆，重庆大学附属肿瘤医院：泌尿外科
2.400030 重庆，重庆大学附属肿瘤医院：健康体检与肿瘤筛查中心
3.150086 广州，中山大学肿瘤防治中心泌尿外科
- 作者简介：
[刘南，E-mail: 1054567372@qq.com LIU Nan, E-mail: 1054567372@qq.com
- 基金信息：
DOI：10.16016/j.1000-5404.202106157
中图分类号： R394.2;R730.23;R737.14收稿：2021-06-20，
修回：2021-09-27，
纸质出版：2021-12-15
- 稿件说明：
移动端阅览
袁刚军, 韩娜, 谭星亮, 等. 肿瘤微环境中M2巨噬细胞调控CLDN10通路促进膀胱癌细胞的上皮-间质转化[J]. 第三军医大学学报, 2021,43(23):2525-2531.
Gangjun YUAN, Na HAN, Xingliang TAN, et al. M2 macrophages promotes bladder cancer EMT through CLDN10 involved signaling pathway in tumor micro-environment[J]. Journal of Third Military Medical University, 2021, 43(23): 2525-2531.
袁刚军, 韩娜, 谭星亮, 等. 肿瘤微环境中M2巨噬细胞调控CLDN10通路促进膀胱癌细胞的上皮-间质转化[J]. 第三军医大学学报, 2021,43(23):2525-2531. DOI： 10.16016/j.1000-5404.202106157.
Gangjun YUAN, Na HAN, Xingliang TAN, et al. M2 macrophages promotes bladder cancer EMT through CLDN10 involved signaling pathway in tumor micro-environment[J]. Journal of Third Military Medical University, 2021, 43(23): 2525-2531. DOI： 10.16016/j.1000-5404.202106157.
摘要
目的
2
探讨膀胱癌微环境中M2巨噬细胞通过CLDN10信号通路对膀胱癌细胞上皮-间质转化(epithelial-mesenchymal transition，EMT)的调控作用及其机制。
方法
2
收集2020年3-9月重庆大学附属肿瘤医院收治的10例膀胱癌患者的新鲜癌组织及癌旁组织标本，免疫组化观测巨噬细胞表面标志物在膀胱癌组织中的表达；对癌和癌旁组织进行转录组测序，筛选出受巨噬细胞调控的潜在基因。采用CCK-8、细胞克隆、Western blot等方法观测CLDN10对膀胱癌细胞生长和增殖的作用。
结果
2
巨噬细胞特征性分子CD68和M2型巨噬细胞CD163分子在膀胱癌组织中表达增加。对基因测序结果分析后发现CLDN10基因在膀胱癌组织中表达最显著，对膀胱癌组织免疫组化结果行免疫评分后发现CLDN10的表达与巨噬细胞在膀胱癌组织中的浸润呈正相关。Western blot检测结果表明膀胱癌组织中CLDN10蛋白的表达水平较癌旁组织高(
P
<
0.05)。敲低CLDN10的表达后，与对照组相比，生长曲线结果表明膀胱癌细胞生长能力下降，细胞克隆形成实验结果表明膀胱癌细胞形成细胞克隆数目降低(198.0±10.3
vs
145.0±8.4，
P
<
0.05)，Western blot检测结果表明EMT相关指标蛋白snail、twist、vimentin的表达水平降低，而E-cadherin的表达水平升高(
P
<
0.05)。
结论
2
巨噬细胞上调膀胱癌细胞CLDN10的表达促进膀胱癌细胞EMT的发生。
Abstract
Objective
2
To investigate the role and mechanism on how M2 macrophages promote epithelial-mesenchymal transition (EMT) of bladder cancer cells
via
clauding10 (CLDN10)-mediated signaling pathway.
Methods
2
Ten pairs of fresh bladder cancer tissues and corresponding para-tumor tissues were collected in Chongqing University Cancer Hospital during March and September 2020. Immunohistochemical (IHC) assay was used to detect the expression of macrophages' membrane markers. The genes regulated by macrophages were screen out with transcriptome sequencing together with immune scores based on IHC assay in bladder tissues. CCK-8 assay
cellular colony and Western blotting were employed to observe the effect of CLDN10 on the growth and proliferation of bladder cancer cells.
Results
2
Macrophages' characteristic marker CD68 and M2 macrophages' CD163 were highly expressed in bladder cancer tissues. Gene sequencing indicated that CLDN10 was significantly expressed in the tumor tissues
and its expression was positively correlated with the infiltration of macrophages in bladder tissues. The Results of Western blotting showed that the CLDN10 expression were higher in cancer tissues compared to adjacent normal tissues (
P
<
0.05). Knockdown of CLDN10 decreased the growth ability of T24 cells and decreased the number of colonies than the untreated cells (198.0±10.3
vs
145.0±8.4
P
<
0.05). Additionally
the protein levels of snail
twist and vimentin were significantly decreased
whereas that of Ecadherin was increased after CLDN10 knockdown.
Conclusion
2
Macrophages upregulate CLDN10 expression in bladder cancer cells
and thus promotes EMT and progression of the cancer cells.
关键词
Keywords
references
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