Anti-Metastatic and Anti-Invasion Effects of a Specific Anti-MUC18 scFv Antibody on Breast Cancer Cells

• Published in: Applied biochemistry and biotechnology Vol. 181; no. 1; pp. 379 - 390
• Main Authors: Mohammadi, Mozafar, Nejatollahi, Foroogh, Ghasemi, Younes, Faraji, Sayyid Nooreddin
• Format: Journal Article
• Language: English
• Published: New York Springer US 2017; Springer Nature B.V
• Subjects: Binding Sites; Biochemistry; Biotechnology; Breast cancer; Breast Neoplasms - genetics; Breast Neoplasms - immunology; Breast Neoplasms - therapy; CD146 Antigen - genetics; CD146 Antigen - immunology; Cell adhesion & migration; Cell Line, Tumor; Cell Movement - immunology; Chemistry; Chemistry and Materials Science; Computer Simulation; Epitopes - genetics; Epitopes - immunology; Female; Flow Cytometry; Gene Expression Regulation, Neoplastic - genetics; Gene Expression Regulation, Neoplastic - immunology; Humans; Ligands; Neoplasm Invasiveness - immunology; Protein Binding; Proteins; Single-Chain Antibodies - immunology; Single-Chain Antibodies - therapeutic use; Wnt-5a Protein - genetics; Wnt-5a Protein - immunology; Protein docking; Wnt-5a; scFv; MUC18; Molecular modeling; Metastases
• ISSN: 0273-2289; 1559-0291
• DOI: 10.1007/s12010-016-2218-1

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.