title: Anti-Metastatic and Anti-Invasion Effects of a Specific Anti-MUC18 scFv Antibody on Breast Cancer Cells.
abstract: Breast cancer is the most common malignancy in women. Altered expression of MUC18, a cell surface receptor, and its interaction with Wnt-5a as its ligand, affects the motility and invasiveness of breast cancer cells. In this study, we explored the Wnt-5a binding site and designed an antigenic epitope on the MUC18 receptor using in silico methods. A specific single-chain variable fragment (scFv) was isolated against the epitope by several panning processes. The binding ability of the scFv to the related epitope was evaluated in ELISA and flow cytometry. The inhibitory effects of the selected scFv on MUC18 positive cell line, MDA-MB231, was assessed by migration and invasion assays. The results demonstrated isolation of specific scFv with frequency of 40 % which showed significant binding with the epitope in both ELISA and fluorescence-activated cell sorting (FACS) analyses. The antibody inhibited the migration (76 %) and invasion (67 %) of MUC18 positive cell line. The results suggest the specific anti-MUC18 scFv as an effective antibody for breast cancer immunotherapy.
authors: Faculty of advanced medical sciences and technologies, Shiraz University of Medical Sciences, Shiraz, Iran.|Recombinant antibody laboratory, Dept. of immunology, Shiraz University of Medical Sciences, Shiraz, Iran.
authors: Mozafar
authors: M
authors: Mohammadi
authors: Recombinant antibody laboratory, Dept. of immunology, Shiraz University of Medical Sciences, Shiraz, Iran. nejatollaf@sums.ac.ir.|Shiraz HIV/AIDS research center, Shiraz University of Medical Sciences, Shiraz, Iran. nejatollaf@sums.ac.ir.
authors: Foroogh
authors: F
authors: Nejatollahi
authors: Faculty of advanced medical sciences and technologies, Shiraz University of Medical Sciences, Shiraz, Iran.|Department of Pharmaceutical Biotechnology; School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.
authors: Younes
authors: Y
authors: Ghasemi
authors: Faculty of advanced medical sciences and technologies, Shiraz University of Medical Sciences, Shiraz, Iran.|Recombinant antibody laboratory, Dept. of immunology, Shiraz University of Medical Sciences, Shiraz, Iran.
authors: Sayyid Nooreddin
authors: SN
authors: Faraji
mesh_terms: D001665:Binding Sites; D001943:Breast Neoplasms / Q000235:genetics / Q000276:immunology* / Q000628:therapy; D051929:CD146 Antigen / Q000235:genetics / Q000276:immunology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000276:immunology; D003198:Computer Simulation; D000939:Epitopes / Q000235:genetics / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics / Q000276:immunology; D006801:Humans; D009361:Neoplasm Invasiveness / Q000276:immunology; D011485:Protein Binding; D057127:Single-Chain Antibodies / Q000276:immunology / Q000627:therapeutic use*; D000071818:Wnt-5a Protein / Q000235:genetics / Q000276:immunology*
chemical_list: D051929:CD146 Antigen; D000939:Epitopes; C497902:MCAM protein, human; D057127:Single-Chain Antibodies; C085389:WNT5A protein, human; D000071818:Wnt-5a Protein
keywords: MUC18; Metastases; Molecular modeling; Protein docking; Wnt-5a; scFv