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Identification and angiogenic role of the novel tumor endothelial marker CLEC14A

Oncogene volume 31, pages 293–305 (2012)Cite this article

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.

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Acknowledgements

We thank Professor Maria Grazia Lampugnani, IFOM—FIRC Institute for Molecular Oncology, Milan, for the gift of the BU9 anti-human VE cadherin mouse monoclonal antibody; and Dr Raj Mehta, Cancer Research Technology for helpful discussions. This work was supported by program grant number C4719/A6766 and project grant number C4719/A9601 from the Cancer Research UK to RB. RB and GBN acknowledge financial support from the British Heart Foundation. Umbilical cords were collected with the assistance of the Birmingham Women's Health Care NHS Trust.

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Author notes

  1. M Mura, R K Swain and X Zhuang: These authors contributed equally to this work and should be considered joint first authors.

Authors and Affiliations

  1. 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

    M Mura, R K Swain, X Zhuang, H Vorschmitt, S Durant, J F J Beesley, J M J Herbert & R Bicknell

  2. Liver Laboratories, Institute for Biomedical Research, School of Immunity and Infection, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK

    G Reynolds

  3. Cancer Research UK Angiogenesis Group, Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK

    H Sheldon, M Andre, S Sanderson & R Bicknell

  4. Centre for Cardiovascular Sciences, School of Clinical and Experimental Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK

    K Glen, N-T Luu, H M McGettrick & G B Nash

  5. School of Biosciences, University of Birmingham, Edgbaston, Birmingham, UK

    P Antczak & F Falciani

  6. Neurodegeneration and Repair Group, School of Clinical and Experimental Medicine, College of Medicine and Dentistry, University of Birmingham, Birmingham, UK

    Z S Nagy

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Correspondence to R Bicknell.

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Competing interests

RB, MM and XZ are named inventors of a patent filed by Cancer Research UK in the United States Patent and trademark Office on 3 September 2009 under No. 61/239,584, bearing Attorney Docket No. P0357.70004US00 and entitled ‘Inhibitors’. All the other authors declare no conflict of interest.

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Mura, M., Swain, R., Zhuang, X. et al. Identification and angiogenic role of the novel tumor endothelial marker CLEC14A. Oncogene 31, 293–305 (2012). https://doi.org/10.1038/onc.2011.233

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