title: Human antibodies targeting the C-type lectin-like domain of the tumor endothelial cell marker clec14a regulate angiogenic properties in vitro.
abstract: It has been suggested that clec14a may be involved in tumor angiogenesis. However, a molecular mechanism has not been clearly identified. In this study, we show for the first time that C-type lectin-like domain (CTLD) of clec14a may be important for regulating cell migration and filopodia formation. Using phage display technology, recombinant human antibodies specific to the CTLDs of human and mouse clec14a (clec14a-CTLD (immunoglobulin G) IgG) were selected. Functional assays using the antibodies showed that clec14a-CTLD IgGs specifically blocked endothelial cell migration and tube formation without affecting cell viability or activation. Further, clec14a-CTLD IgGs inhibited clec14a-mediated cell-cell contact by blocking interaction between CTLDs. Finally, clec14a cross-linking by the clec14a-CTLD IgGs significantly downregulated clec14a expression on the surface of endothelial cells. These results strongly suggest that the clec14a-CTLD may be a key domain in angiogenesis, and that clec14a-CTLD IgGs specifically inhibit angiogenesis by modulating CTLD-mediated cell interactions and clec14a expression on the surface of endothelial cells.
authors: Laboratory of Molecular Cancer Therapeutics, Scripps Korea Antibody Institute, Chuncheon, Korea.
authors: M K
authors: MK
authors: Ki
authors: M H
authors: MH
authors: Jeoung
authors: J R
authors: JR
authors: Choi
authors: S-S
authors: SS
authors: Rho
authors: Y-G
authors: YG
authors: Kwon
authors: H
authors: H
authors: Shim
authors: J
authors: J
authors: Chung
authors: H J
authors: HJ
authors: Hong
authors: B D
authors: BD
authors: Song
authors: S
authors: S
authors: Lee
mesh_terms: D000818:Animals; D000918:Antibody Specificity; D014408:Biomarkers, Tumor / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism*; D002450:Cell Communication; D002465:Cell Movement; D002470:Cell Survival; D015536:Down-Regulation; D057809:HEK293 Cells; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry / Q000276:immunology*; D037181:Lectins, C-Type / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism*; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D011554:Pseudopodia / Q000378:metabolism; D057127:Single-Chain Antibodies / Q000737:chemistry / Q000276:immunology
chemical_list: D014408:Biomarkers, Tumor; C570898:CLEC14A protein, human; D015815:Cell Adhesion Molecules; C555817:Clec14a protein, mouse; D007074:Immunoglobulin G; D037181:Lectins, C-Type; D008565:Membrane Proteins; D057127:Single-Chain Antibodies
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