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基质金属蛋白酶组织抑制因子-1（TIMP-1）和CD82，一种用于胰腺导管腺癌（PDAC）的有前景的联合评估标志物。

TIMP-1 and CD82, a promising combined evaluation marker for PDAC.

作者信息

Zhang Jiexin, Wu Tijun, Zhan Shanshan, Qiao Nan, Zhang Xu, Zhu Yunxia, Yang Nan, Sun Yujie, Zhang Xin A, Bleich David, Han Xiao

机构信息

Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, Nanjing, China.

出版信息

Oncotarget. 2017 Jan 24;8(4):6496-6512. doi: 10.18632/oncotarget.14133.

DOI:10.18632/oncotarget.14133
PMID:28030805
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5351648/
Abstract

Tissue inhibitor of metalloproteinases-1 (TIMP-1) is a widely secreted protein that regulates cell motility, proliferation, and apoptosis. Although it is recognized that TIMP-1-tetraspanin CD63 regulates epithelial cell apoptosis and proliferation, how TIMP-1 controls cell motility is not well understood. In this study, we identify tetraspanin CD82 (also called KAI1) as a component of the promiscuous TIMP-1 interacting protein complex on cell surface of human pancreatic adenocarcinoma cells. CD82 directly binds to TIMP-1 N-terminal region through its large extracellular loop and co-localizes with TIMP-1 in both cancer cell lines and clinical samples. Moreover, CD82 facilitates membrane-bound TIMP-1 endocytosis, which significantly contributes to the anti-migration effect of TIMP-1. CD82 silencing partially eliminates these functions. TIMP-1 and CD82 expression status in patients with pancreatic ductal adenocarcinoma (PDAC) might demonstrate future usefulness as a differentiation marker and give us new insight into tumorigenic metastatic potential.

摘要

金属蛋白酶组织抑制剂-1（TIMP-1）是一种广泛分泌的蛋白质，可调节细胞运动、增殖和凋亡。尽管人们认识到TIMP-1-四跨膜蛋白CD63可调节上皮细胞凋亡和增殖，但TIMP-1如何控制细胞运动尚不清楚。在本研究中，我们确定四跨膜蛋白CD82（也称为KAI1）是人类胰腺腺癌细胞表面混杂的TIMP-1相互作用蛋白复合物的一个组成部分。CD82通过其大的细胞外环直接与TIMP-1的N端区域结合，并在癌细胞系和临床样本中与TIMP-1共定位。此外，CD82促进膜结合的TIMP-1内吞作用，这对TIMP-1的抗迁移作用有显著贡献。CD82沉默可部分消除这些功能。胰腺导管腺癌（PDAC）患者中TIMP-1和CD82的表达状态可能作为一种分化标志物显示出未来的应用价值，并为我们提供有关肿瘤发生转移潜能的新见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/578a/5351648/ffdc4626007f/oncotarget-08-6496-g008.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/578a/5351648/e81dfc5ac5af/oncotarget-08-6496-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/578a/5351648/ffdc4626007f/oncotarget-08-6496-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/578a/5351648/77556526677c/oncotarget-08-6496-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/578a/5351648/dfe6e5268492/oncotarget-08-6496-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/578a/5351648/144e858df4a9/oncotarget-08-6496-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/578a/5351648/88ebab875ec6/oncotarget-08-6496-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/578a/5351648/82ee70f0d241/oncotarget-08-6496-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/578a/5351648/c813a43a9e7a/oncotarget-08-6496-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/578a/5351648/e81dfc5ac5af/oncotarget-08-6496-g007.jpg
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