title: Identification and angiogenic role of the novel tumor endothelial marker CLEC14A.
abstract: Tumor endothelial markers (TEMs) that are highly expressed in human tumor vasculature compared with vasculature in normal tissue hold clear therapeutic potential. We report that the C-type lectin CLEC14A is a novel TEM. Immunohistochemical and immunofluorescence staining of tissue arrays has shown that CLEC14A is strongly expressed in tumor vasculature when compared with vessels in normal tissue. CLEC14A overexpression in tumor vessels was seen in a wide range of solid tumor types. Functional studies showed that CLEC14A induces filopodia and facilitates endothelial migration, tube formation and vascular development in zebrafish that is, CLEC14A regulates pro-angiogenic phenotypes. CLEC14A antisera inhibited cell migration and tube formation, suggesting that anti-CLEC14A antibodies may have anti-angiogenic activity. Finally, in endothelial cultures, expression of CLEC14A increased at low shear stress, and we hypothesize that low shear stress due to poor blood flow in the disorganized tumor vasculature induces expression of CLEC14A on tumor vessels and pro-angiogenic phenotypes.
authors.affiliation: Angiogenesis Group, Centre for Cardiovascular Sciences, Institute for Biomedical Research, Schools of Immunity and Infection and Cancer Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
authors.forename: M
authors.initials: M
authors.lastname: Mura
authors.forename: R K
authors.initials: RK
authors.lastname: Swain
authors.forename: X
authors.initials: X
authors.lastname: Zhuang
authors.forename: H
authors.initials: H
authors.lastname: Vorschmitt
authors.forename: G
authors.initials: G
authors.lastname: Reynolds
authors.forename: S
authors.initials: S
authors.lastname: Durant
authors.forename: J F J
authors.initials: JF
authors.lastname: Beesley
authors.forename: J M J
authors.initials: JM
authors.lastname: Herbert
authors.forename: H
authors.initials: H
authors.lastname: Sheldon
authors.forename: M
authors.initials: M
authors.lastname: Andre
authors.forename: S
authors.initials: S
authors.lastname: Sanderson
authors.forename: K
authors.initials: K
authors.lastname: Glen
authors.forename: N-T
authors.initials: NT
authors.lastname: Luu
authors.forename: H M
authors.initials: HM
authors.lastname: McGettrick
authors.forename: P
authors.initials: P
authors.lastname: Antczak
authors.forename: F
authors.initials: F
authors.lastname: Falciani
authors.forename: G B
authors.initials: GB
authors.lastname: Nash
authors.forename: Z S
authors.initials: ZS
authors.lastname: Nagy
authors.forename: R
authors.initials: R
authors.lastname: Bicknell
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D001943:Breast Neoplasms / Q000098:blood supply / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D004730:Endothelium, Vascular / Q000378:metabolism*; D005260:Female; D006801:Humans; D037181:Lectins, C-Type / Q000235:genetics / Q000378:metabolism*; D008113:Liver Neoplasms / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D008297:Male; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000098:blood supply / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000098:blood supply / Q000378:metabolism; D011554:Pseudopodia / Q000378:metabolism; D001749:Urinary Bladder Neoplasms / Q000098:blood supply / Q000378:metabolism; D015027:Zebrafish
chemical_list: D014408:Biomarkers, Tumor; C570898:CLEC14A protein, human; D015815:Cell Adhesion Molecules; D037181:Lectins, C-Type