Validation of an anti-sphingosine-1-phosphate antibody as a potential therapeutic in reducing growth, invasion, and angiogenesis in multiple tumor lineages

Barbara Visentin, John A. Vekich, Bradley J. Sibbald, Amy L. Cavalli, Kelli M. Moreno, Rosalia G. Matteo, William A. Garland, Yiling Lu, Shuangxing Yu, Hassan S. Hall, Vikas Kundra, Gordon B. Mills, Roger A. Sabbadini

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    374 Scopus citations

    Abstract

    S1P has been proposed to contribute to cancer progression by regulating tumor proliferation, invasion, and angiogenesis. We developed a biospecific monoclonal antibody to S1P to investigate its role in tumorigenesis. The anti-S1P mAb substantially reduced tumor progression and in some cases eliminated measurable tumors in murine xenograft and allograft models. Tumor growth inhibition was attributed to antiangiogenic and antitumorigenic effects of the antibody. The anti-S1P mAb blocked EC migration and resulting capillary formation, inhibited blood vessel formation induced by VEGF and bFGF, and arrested tumor-associated angiogenesis. The anti-S1P mAb also neutralized S1P-induced proliferation, release of proangiogenic cytokines, and the ability of S1P to protect tumor cells from apoptosis in several tumor cell lines, validating S1P as a target for therapy.

    Original languageEnglish (US)
    Pages (from-to)225-238
    Number of pages14
    JournalCancer Cell
    Volume9
    Issue number3
    DOIs
    StatePublished - Mar 1 2006

    ASJC Scopus subject areas

    • Oncology
    • Cell Biology
    • Cancer Research

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    Visentin, B., Vekich, J. A., Sibbald, B. J., Cavalli, A. L., Moreno, K. M., Matteo, R. G., Garland, W. A., Lu, Y., Yu, S., Hall, H. S., Kundra, V., Mills, G. B., & Sabbadini, R. A. (2006). Validation of an anti-sphingosine-1-phosphate antibody as a potential therapeutic in reducing growth, invasion, and angiogenesis in multiple tumor lineages. Cancer Cell, 9(3), 225-238. https://doi.org/10.1016/j.ccr.2006.02.023