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Claudins-3、-4 和 -7 在前列腺腺癌中的免疫表达。

Immunoexpression of Claudins -3, -4 and -7 in prostate adenocarcinomas.

机构信息

Department of Pathology, University of Medicine and Pharmacy of Craiova, Romania;

出版信息

Rom J Morphol Embryol. 2023 Apr-Jun;64(2):165-171. doi: 10.47162/RJME.64.2.06.

DOI:10.47162/RJME.64.2.06
PMID:37518873
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10520377/
Abstract

Claudins are a family of essential tight junction proteins, abnormally expressed in human carcinomas. The studies that indicated the involvement of claudins in tumor biology and progression suggest the possibility of their utility as markers for diagnosis or prognosis, but also as possible targets for therapy. We investigated 50 prostate adenocarcinomas (PAs) for which we followed the expression of Claudins -3, -4 and -7 in relation to International Society of Urological Pathology (ISUP) grades. We observed the positivity for Claudin-3, Claudin-4, and Claudin-7 in 76%, 74% and 46% of cases. Analysis of the immunoexpression pattern revealed the cytoplasmic and nuclear translocation for Claudins -3 and -4, and only cytoplasmic for Claudin-7. For all claudins investigated, we noted a final staining score with significantly higher values or at the limit of statistical significance for PA belonging to ISUP groups 1-4. The internalization of Claudins -3, -4 and -7 expression, regardless of the degree of PA, indicates their involvement in prostate carcinogenesis. In addition, the similar immunoexpression patterns of the three investigated claudins and their positive linear correlation suggest a coordinated regulation and indicate the possibility of a targeted treatment strategy.

摘要

紧密连接蛋白家族成员 Claudin 在人类癌组织中异常表达。Claudin 在肿瘤生物学和进展中的作用的研究提示 Claudin 可作为诊断或预后标志物,并可能成为治疗靶点。我们研究了 50 例前列腺腺癌(PA),分析 Claudin-3、Claudin-4 和 Claudin-7 的表达与国际泌尿病理学会(ISUP)分级的关系。我们观察到 Claudin-3、Claudin-4 和 Claudin-7 在 76%、74%和 46%的病例中呈阳性。免疫组化结果显示 Claudin-3 和 Claudin-4 发生了细胞质和核转位,而 Claudin-7 仅发生了细胞质转位。对于所有研究的 Claudin,我们发现 ISUP 1-4 级 PA 的终末染色评分明显较高或具有统计学意义。Claudin-3、Claudin-4 和 Claudin-7 表达的内化,无论 PA 程度如何,都表明其参与了前列腺癌的发生。此外,三种 Claudin 的免疫组化表达模式相似,且呈正线性相关,提示 Claudin 的表达受到协调调控,并提示靶向治疗策略的可能性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fcc8/10520377/d1a7ecfd8414/RJME-64-2-165-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fcc8/10520377/4720293fadf3/RJME-64-2-165-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fcc8/10520377/e14affddae2a/RJME-64-2-165-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fcc8/10520377/bdca57e53287/RJME-64-2-165-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fcc8/10520377/d1a7ecfd8414/RJME-64-2-165-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fcc8/10520377/4720293fadf3/RJME-64-2-165-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fcc8/10520377/e14affddae2a/RJME-64-2-165-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fcc8/10520377/bdca57e53287/RJME-64-2-165-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fcc8/10520377/d1a7ecfd8414/RJME-64-2-165-fig4.jpg

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本文引用的文献

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Knocking down claudin receptors leads to a decrease in prostate cancer cell migration, cell growth, cell viability and clonogenic cell survival.敲低紧密连接蛋白受体会导致前列腺癌细胞迁移、细胞生长、细胞活力和克隆细胞存活率降低。
Mol Biomed. 2021 Oct 10;2(1):31. doi: 10.1186/s43556-021-00053-0.
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Context-Dependent Roles of Claudins in Tumorigenesis.紧密连接蛋白在肿瘤发生中的上下文依赖作用。
Front Oncol. 2021 Jul 20;11:676781. doi: 10.3389/fonc.2021.676781. eCollection 2021.
3
Role of Nuclear Claudin-4 in Renal Cell Carcinoma.核 Claudin-4 在肾细胞癌中的作用。
Int J Mol Sci. 2020 Nov 6;21(21):8340. doi: 10.3390/ijms21218340.
4
Role of Enterotoxin on YAP Activation in Colonic Sessile Serrated Adenoma/ Polyps with Dysplasia.肠毒素在伴异型增生的结直肠无蒂锯齿状腺瘤/息肉中对 YAP 激活的作用。
Int J Mol Sci. 2020 May 28;21(11):3840. doi: 10.3390/ijms21113840.
5
Potential for Tight Junction Protein-Directed Drug Development Using Claudin Binders and Angubindin-1.利用 Claudin 结合物和 Angubindin-1 开发紧密连接蛋白导向药物的潜力。
Int J Mol Sci. 2019 Aug 17;20(16):4016. doi: 10.3390/ijms20164016.
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Expression and significance of PTEN and Claudin-3 in prostate cancer.PTEN和Claudin-3在前列腺癌中的表达及意义
Oncol Lett. 2019 Jun;17(6):5628-5634. doi: 10.3892/ol.2019.10212. Epub 2019 Apr 3.
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[Claudin-3 expression in colorectal carcinoma and its significance].[Claudin-3在结直肠癌中的表达及其意义]
Nan Fang Yi Ke Da Xue Xue Bao. 2017 Jan 20;37(1):63-67. doi: 10.3969/j.issn.1673-4254.2017.01.11.
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Claudin proteins, outside-in signaling, and carcinogenesis.闭合蛋白、外向内信号传导与致癌作用。
Pflugers Arch. 2017 Jan;469(1):69-75. doi: 10.1007/s00424-016-1919-1. Epub 2016 Dec 17.
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The role of claudins in cancer metastasis.紧密连接蛋白在癌症转移中的作用。
Oncogene. 2017 Mar 2;36(9):1176-1190. doi: 10.1038/onc.2016.289. Epub 2016 Aug 15.
10
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Am J Surg Pathol. 2016 Feb;40(2):244-52. doi: 10.1097/PAS.0000000000000530.