ADAM8 expression is associated with increased invasiveness and reduced patient survival in pancreatic cancer
| Autor: | S. Osinsky, Hany Kayed, Jörg Kleeff, Daniel Hartmann, H. Friess, N. Valkovskaya, Klaus Felix, Nathalia A. Giese |
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| Rok vydání: | 2007 |
| Předmět: |
Adult
ADAM8 pancreatic cancer Biology medicine.disease_cause survival Cell Line Tumor Pancreatic cancer medicine Humans Gene silencing Neoplasm Invasiveness RNA Messenger RNA Small Interfering Cell Proliferation Cell growth Membrane Proteins Articles Cell Biology Transfection Middle Aged invasion medicine.disease Survival Analysis Molecular biology Cell Hypoxia Protein Structure Tertiary Gene Expression Regulation Neoplastic Pancreatic Neoplasms ADAM Proteins Membrane protein Spectrometry Mass Matrix-Assisted Laser Desorption-Ionization Cancer cell Molecular Medicine Carcinogenesis Protein Processing Post-Translational Carcinoma Pancreatic Ductal |
| Zdroj: | Journal of Cellular and Molecular Medicine |
| ISSN: | 1582-4934 1582-1838 |
| DOI: | 10.1111/j.1582-4934.2007.00082.x |
| Popis: | ADAM8 belongs to a family of transmembrane proteins implicated in cell–cell interactions, proteolysis of membrane proteins, and various aspects of carcinogenesis. In the present study, we aimed to evaluate the expression and function of ADAM8 in pancreatic cancer. ADAM8 mRNA levels were analysed by quantitative RT-PCR and correlated to patient survival. Immunohistochemistry was performed to localize ADAM8 in pancreatic tis-sues. Silencing of ADAM8 expression was carried out by transfection with specific siRNA oligonucleotides. Cell growth and invasion assays were used to assess the functional consequences of ADAM8 silencing. SELDI-TOF-MS was performed to detect the proteolytic activity of ADAM8 in pancreatic cancer cells. ADAM8 mRNA was significantly overexpressed in pancreatic ductal adenocarcinoma (PDAC) compared with normal pancreatic tissues (5.3-fold increase; P= 0.0008), and high ADAM8 mRNA and protein expression levels correlated with reduced survival time of PDAC patients (P= 0.048 and P= 0.065, respectively). Silencing of ADAM8 expression did not significantly influence pancreatic cancer cell growth but suppressed invasiveness. In addition, decreased proteolytic activity was measured in cell culture supernatants following silencing of ADAM8. In conclusion, ADAM8 is overexpressed in PDAC, influences cancer cell invasiveness and correlates with reduced survival, suggesting that ADAM8 might be a potential target in pancreatic cancer therapy. |
| Databáze: | OpenAIRE |
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