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https://doi.org/10.1371/journal.pone.0167860
Title: | An anti-human lutheran glycoprotein phage antibody inhibits cell migration on laminin-511: Epitope mapping of the antibody | Authors: | Enomoto-Okawa Y. Maeda Y. Harashima N. Sugawara Y. Katagiri F. Hozumi K. Hui K.M. Nomizu M. Ito Y. Kikkawa Y. |
Keywords: | autoantibody glycoprotein laminin 10 lutheran glycoprotein monoclonal antibody unclassified drug blood group Lutheran system epitope glycoprotein monoclonal antibody peptide library protein binding single chain fragment variable antibody adult animal tissue Article cancer growth cell migration clinical article controlled study enzyme inhibition epitope mapping human human tissue limit of quantitation liver cell carcinoma male metastasis mouse mutagenesis nonhuman pathogenesis periplasm protein binding protein function protein localization amino acid sequence blood group Lutheran system cell motion cell surface display chemistry drug effects enzyme linked immunosorbent assay epitope mapping immunology isolation and purification peptide library procedures protein domain tumor cell line Amino Acid Sequence Antibodies, Monoclonal Cell Line, Tumor Cell Movement Cell Surface Display Techniques Enzyme-Linked Immunosorbent Assay Epitope Mapping Epitopes Glycoproteins Humans Lutheran Blood-Group System Peptide Library Protein Binding Protein Interaction Domains and Motifs Single-Chain Antibodies |
Issue Date: | 2017 | Publisher: | Public Library of Science | Citation: | Enomoto-Okawa Y., Maeda Y., Harashima N., Sugawara Y., Katagiri F., Hozumi K., Hui K.M., Nomizu M., Ito Y., Kikkawa Y. (2017). An anti-human lutheran glycoprotein phage antibody inhibits cell migration on laminin-511: Epitope mapping of the antibody. PLoS ONE 12 (1) : 167860. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pone.0167860 | Abstract: | The Lutheran glycoprotein (Lu), also known as basal cell adhesion molecule (B-CAM), is an Ig superfamily (IgSF) transmembrane receptor for laminin ?5. Although Lu is not present in normal hepatocytes, its expression is significantly increased in hepatocellular carcinoma (HCC). In this study, we isolated thirteen phage antibodies to Lu from a phage library of peripheral blood from HCC patients, suggesting that these patients produced autoantibodies against endogenous Lu. To characterize the phage antibodies, we determined the Lu domains they recognize. The extracellular domain of Lu contains five IgSF domains, D1-D2- D3-D4-D5. The epitope of one phage antibody (A7) was localized to the D5 domain. The other phage antibodies recognized the D2 domain, which is also recognized by a function blocking mouse monoclonal antibody. One of the antibodies to D2 (C7) inhibited the binding of Lu to ligand, and it also prevented tumor cell migration on laminin-511 (LM-511). However, the C7 scFv purified from the periplasm fraction of bacteria did not exhibit the inhibitory effects, indicating that the scFv form could not sterically inhibit the binding of Lu to LM-511. We also identified the amino acid residues that form the epitope recognized by the C7 phage antibody. Mutagenesis studies showed that Arg247 is necessary for forming the epitope. The C7 phage antibody and its epitope may be useful for developing drugs to prevent HCC progression and/or metastasis. © 2016 Enomoto-Okawa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. | Source Title: | PLoS ONE | URI: | https://scholarbank.nus.edu.sg/handle/10635/166029 | ISSN: | 19326203 | DOI: | 10.1371/journal.pone.0167860 |
Appears in Collections: | Elements Staff Publications |
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