title: A8, an anti-uPA agonistic antibody, promotes metastasis of cancer cells via ERK pathway.
abstract: Urokinase-type plasminogen activator (uPA) and uPA receptor (uPAR) are expressed in many tumors and have been reported to be correlated to protein expression and poor prognosis in malignant tumors. In a previous study, we reported on the selection of human single-chain variable fragment (scFv) A8 specific to uPA from phage-displayed human naïve scFv library. In this study, scFv A8 was converted to minibody form and evaluated for its functional ability on the uPA system involved in cellular signaling and cancer cell metastasis. A8 minibody increased enzyme activity of uPA and enhanced the migration and invasion of HT1080 colon cancer cells in a dose-dependent manner. A8 increased ERK phosphorylation, and enhanced migration was blocked by U0126, but not by LY0294002, SB2203580, and SP600125. A8 minibody also enhanced migration of MDA-MB231 by mediated expressing surface uPA, but not that of MCF-7 non-expressing surface uPA. Taken together, the A8 anti-uPA antibody is a uPA agonistic antibody, enhancing migration and invasion of cancer cells that express uPA via activation of ERK pathway.
authors.affiliation: 1 Department of Microbiology and Immunology, INJE University College of Medicine , Busan, Republic of Korea.
authors.forename: Hyunkeun
authors.initials: H
authors.lastname: Song
authors.forename: A-Young
authors.initials: AY
authors.lastname: Lee
authors.forename: Hana
authors.initials: H
authors.lastname: Jung
authors.forename: Jae-Hyeog
authors.initials: JH
authors.lastname: Choi
authors.forename: Kughwan
authors.initials: K
authors.lastname: Roh
authors.forename: Sungmin
authors.initials: S
authors.lastname: Ha
authors.forename: Kwang-Dong
authors.initials: KD
authors.lastname: Kim
authors.forename: Ki-Beom
authors.initials: KB
authors.lastname: Bae
authors.forename: Mi Seon
authors.initials: MS
authors.lastname: Kang
authors.forename: SungJae
authors.initials: S
authors.lastname: Park
authors.forename: Il-Whan
authors.initials: IW
authors.lastname: Choi
authors.forename: Su-Kil
authors.initials: SK
authors.lastname: Seo
authors.forename: SaeGwang
authors.initials: S
authors.lastname: Park
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology*; D002465:Cell Movement / Q000276:immunology; D057809:HEK293 Cells; D006801:Humans; D020935:MAP Kinase Signaling System / Q000276:immunology*; D061986:MCF-7 Cells; D009362:Neoplasm Metastasis / Q000276:immunology*; D010766:Phosphorylation / Q000276:immunology; D011956:Receptors, Cell Surface / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*; D057127:Single-Chain Antibodies / Q000276:immunology*; D014407:Tumor Cells, Cultured; D014568:Urokinase-Type Plasminogen Activator / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D011956:Receptors, Cell Surface; D057127:Single-Chain Antibodies; D014568:Urokinase-Type Plasminogen Activator