title: TIMP-1 and CD82, a promising combined evaluation marker for PDAC.
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.
authors.affiliation: Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Jiexin
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, Nanjing, China.
authors.forename: Tijun
authors.initials: T
authors.lastname: Wu
authors.affiliation: Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, Nanjing, China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Zhan
authors.affiliation: Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, Nanjing, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Qiao
authors.affiliation: Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, Nanjing, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, Nanjing, China.
authors.forename: Yunxia
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, Nanjing, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Yang
authors.affiliation: Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, Nanjing, China.
authors.forename: Yujie
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Stephenson Cancer Center and Department of Physiology, University of Oklahoma Health Science Center, Oklahoma, OK, USA.
authors.forename: Xin A
authors.initials: XA
authors.lastname: Zhang
authors.affiliation: Rutgers New Jersey Medical School, Newark, NJ, USA.
authors.forename: David
authors.initials: D
authors.lastname: Bleich
authors.affiliation: Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, Nanjing, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Han
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics / Q000378:metabolism* / Q000556:secondary; D002462:Cell Membrane / Q000378:metabolism; D002465:Cell Movement; D004705:Endocytosis; D005260:Female; D006801:Humans; D051861:Kangai-1 Protein / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D061986:MCF-7 Cells; D008297:Male; D008875:Middle Aged; D062105:Molecular Docking Simulation; D009361:Neoplasm Invasiveness; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D021381:Protein Transport; D034622:RNA Interference; D013997:Time Factors; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
chemical_list: D014408:Biomarkers, Tumor; C497688:CD82 protein, human; D051861:Kangai-1 Protein; C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1
keywords: CD82; PDAC; TIMP-1; cell motility; interaction