Oncotarget

Research Papers:

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

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

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Oncotarget. 2017; 8:6496-6512. https://doi.org/10.18632/oncotarget.14133

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Abstract

Jiexin Zhang1,*, Tijun Wu2,*, Shanshan Zhan2, Nan Qiao2, Xu Zhang2, Yunxia Zhu2, Nan Yang2, Yujie Sun2, Xin A. Zhang3, David Bleich4, Xiao Han2

1Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China

2Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, Nanjing, China

3Stephenson Cancer Center and Department of Physiology, University of Oklahoma Health Science Center, Oklahoma, OK, USA

4Rutgers New Jersey Medical School, Newark, NJ, USA

*These authors have contributed equally to this work

Correspondence to:

Xiao Han, email: hanxiao@njmu.edu.cn

Keywords: TIMP-1, CD82, interaction, cell motility, PDAC

Received: March 03, 2016     Accepted: November 11, 2016     Published: December 24, 2016

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.


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