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, Xiao Han

Research output: Contribution to journalArticle

7 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)6496-6512
Number of pages17
JournalOncotarget
Volume8
Issue number4
DOIs
StatePublished - Jan 1 2017

    Fingerprint

All Science Journal Classification (ASJC) codes

  • Oncology

Keywords

  • CD82
  • Cell motility
  • Interaction
  • PDAC
  • TIMP-1

Cite this

Zhang, J., Wu, T., Zhan, S., Qiao, N., Zhang, X., Zhu, Y., Yang, N., Sun, Y., Zhang, X. A., Bleich, D., & Han, X. (2017). TIMP-1 and CD82, a promising combined evaluation marker for PDAC. Oncotarget, 8(4), 6496-6512. https://doi.org/10.18632/oncotarget.14133