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

详细信息    查看全文

• 作者：Mozafar Mohammadi ; Foroogh Nejatollahi…
• 关键词：MUC18 ; Wnt ; 5a ; scFv ; Metastases ; Molecular modeling ; Protein docking
• 刊名：Applied Biochemistry and Biotechnology
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：181
• 期：1
• 页码：379-390
• 全文大小：
• 刊物类别：Chemistry and Materials Science
• 刊物主题：Biotechnology; Biochemistry, general;
• 出版者：Springer US
• ISSN：1559-0291
• 卷排序：181

文摘

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.