title: Downregulation of Extracellular Matrix Metalloproteinase Inducer by scFv-M6-1B9 Intrabody Suppresses Cervical Cancer Invasion Through Inhibition of Urokinase-Type Plasminogen Activator.
abstract: Overexpression of extracellular matrix metalloproteinase inducer (EMMPRIN) accelerates tumor invasion and metastasis via activation of matrix metalloproteinases (MMPs) and urokinase-type plasminogen activator (uPA) expression. The authors were interested in whether the scFv-M6-1B9 intrabody against EMMPRIN that retains EMMPRIN in endoplasmic reticulum could be a potential tool to suppress cervical cancer invasion through inhibition of uPA. The chimeric adenoviral vector Ad5/F35-scFv-M6-1B9 was transferred into human cervical carcinoma HeLa cells to produce the scFv-M6-1B9 intrabody against EMMPRIN. Cell surface expression of EMMPRIN, the membrane-bound uPA, the enzymatic activity of secreted uPA, and the invasion ability were analyzed. The scFv-M6-1B9 intrabody successfully diminished the cell surface expression of EMMPRIN and the membrane-bound uPA on HeLa cells. uPA activity from tissue culture media of EMMPRIN-downregulated HeLa cells was decreased. The invasion ability of HeLa cells harboring scFv-M6-1B9 intrabody was also suppressed. These results suggested that the scFv-M6-1B9 intrabody might represent a potential approach for invasive cervical cancer treatment. The application of scFv-M6-1B9 intrabody in animal experiments and preclinical studies would be investigated further.
authors.affiliation: 1 Division of Clinical Microscopy, Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University , Chiang Mai, Thailand .
authors.forename: Tipattaraporn
authors.initials: T
authors.lastname: Panich
authors.affiliation: 2 Division of Clinical Microbiology, Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University , Chiang Mai, Thailand .|3 Biomedical Technology Research Unit, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency at the Faculty of Associated Medical Sciences, Chiang Mai University , Chiang Mai, Thailand .|4 Center of Biomolecular Therapy and Diagnostic, Faculty of Associated Medical Sciences, Chiang Mai University , Chiang Mai, Thailand .
authors.forename: Khajornsak
authors.initials: K
authors.lastname: Tragoolpua
authors.affiliation: 3 Biomedical Technology Research Unit, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency at the Faculty of Associated Medical Sciences, Chiang Mai University , Chiang Mai, Thailand .|5 Division of Clinical Immunology, Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University , Chiang Mai, Thailand .
authors.forename: Supansa
authors.initials: S
authors.lastname: Pata
authors.affiliation: 3 Biomedical Technology Research Unit, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency at the Faculty of Associated Medical Sciences, Chiang Mai University , Chiang Mai, Thailand .|4 Center of Biomolecular Therapy and Diagnostic, Faculty of Associated Medical Sciences, Chiang Mai University , Chiang Mai, Thailand .|5 Division of Clinical Immunology, Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University , Chiang Mai, Thailand .
authors.forename: Chatchai
authors.initials: C
authors.lastname: Tayapiwatana
authors.affiliation: 1 Division of Clinical Microscopy, Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University , Chiang Mai, Thailand .|3 Biomedical Technology Research Unit, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency at the Faculty of Associated Medical Sciences, Chiang Mai University , Chiang Mai, Thailand .|4 Center of Biomolecular Therapy and Diagnostic, Faculty of Associated Medical Sciences, Chiang Mai University , Chiang Mai, Thailand .
authors.forename: Nutjeera
authors.initials: N
authors.lastname: Intasai
mesh_terms: D000256:Adenoviridae; D051926:Basigin / Q000235:genetics*; D015536:Down-Regulation; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000494:pharmacology; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D020782:Matrix Metalloproteinases / Q000378:metabolism; D009361:Neoplasm Invasiveness; D057127:Single-Chain Antibodies / Q000235:genetics*; D014568:Urokinase-Type Plasminogen Activator / Q000037:antagonists & inhibitors*; D002583:Uterine Cervical Neoplasms / Q000473:pathology* / Q000628:therapy*
chemical_list: C497886:BSG protein, human; D057127:Single-Chain Antibodies; D051926:Basigin; D014568:Urokinase-Type Plasminogen Activator; D020782:Matrix Metalloproteinases
keywords: EMMPRIN; cervical cancer; intrabody; invasion; scFv; uPA