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

AI Article Synopsis

  • Tissue inhibitor of metalloproteinases-1 (TIMP-1) is a secreted protein that impacts cell movement, growth, and programmed cell death, yet its role in cell motility remains unclear.
  • This study discovers that CD82, a tetraspanin, interacts with TIMP-1 in pancreatic cancer cells, binding to TIMP-1's N-terminal region and aiding in its endocytosis, which contributes to TIMP-1's ability to inhibit cell migration.
  • The expression levels of TIMP-1 and CD82 in pancreatic ductal adenocarcinoma (PDAC) patients may serve as potential biomarkers for tumor differentiation and provide insights into cancer spread.

Article 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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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5351648PMC
http://dx.doi.org/10.18632/oncotarget.14133DOI Listing

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