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

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


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.

Keywords: CD82; PDAC; TIMP-1; cell motility; interaction.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / chemistry
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Pancreatic Ductal / genetics
  • Carcinoma, Pancreatic Ductal / metabolism*
  • Carcinoma, Pancreatic Ductal / secondary
  • Cell Membrane / metabolism
  • Cell Movement
  • Endocytosis
  • Female
  • Humans
  • Kangai-1 Protein / chemistry
  • Kangai-1 Protein / genetics
  • Kangai-1 Protein / metabolism*
  • MCF-7 Cells
  • Male
  • Middle Aged
  • Molecular Docking Simulation
  • Neoplasm Invasiveness
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / metabolism*
  • Pancreatic Neoplasms / pathology
  • Protein Binding
  • Protein Interaction Domains and Motifs
  • Protein Transport
  • RNA Interference
  • Time Factors
  • Tissue Inhibitor of Metalloproteinase-1 / chemistry
  • Tissue Inhibitor of Metalloproteinase-1 / genetics
  • Tissue Inhibitor of Metalloproteinase-1 / metabolism*
  • Transfection


  • Biomarkers, Tumor
  • CD82 protein, human
  • Kangai-1 Protein
  • TIMP1 protein, human
  • Tissue Inhibitor of Metalloproteinase-1