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.
Oncogene. 2012 Jan 19;31(3):293-305. doi: 10.1038/onc.2011.233. Epub 2011 Jun 27.
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.
肿瘤内皮标志物（TEMs）在人类肿瘤血管中表达水平高于正常组织中的血管，具有明确的治疗潜力。我们报告称，C 型凝集素 CLEC14A 是一种新型的 TEM。组织芯片的免疫组织化学和免疫荧光染色表明，与正常组织中的血管相比，CLEC14A 在肿瘤血管中强烈表达。在广泛的实体瘤类型中均观察到肿瘤血管中 CLEC14A 的过表达。功能研究表明，CLEC14A 诱导丝状伪足形成，并促进斑马鱼内皮细胞的迁移、管形成和血管发育，即 CLEC14A 调节促血管生成表型。CLEC14A 抗血清抑制细胞迁移和管形成，表明抗 CLEC14A 抗体可能具有抗血管生成活性。最后，在血管内皮细胞培养中，低切应力下 CLEC14A 的表达增加，我们假设紊乱的肿瘤血管中由于血流不良导致的低切应力诱导肿瘤血管上 CLEC14A 的表达和促血管生成表型。
