Vascular endothelial growth factor receptor 3 is involved in tumor angiogenesis and growth

Pirjo Laakkonen, Marika Waltari, Tanja Holopainen, Takashi Takahashi, Bronislaw Pytowski, Philippe Steiner, Daniel Hicklin, Kris Persaud, James R Tonra, Larry Witte, Kari Alitalo

    Research output: Contribution to journalArticleScientificpeer-review


    Vascular endothelial growth factor receptor 3 (VEGFR-3) binds VEGF-C and VEGF-D and is essential for the development of the lymphatic vasculalure. Experimental tumors that overexpress VEGFR-3 ligands induce lymphatic vessel sprouting and enlargement and show enhanced metastasis to regional lymph nodes and beyond, whereas a soluble form of. p VEGFR-3 that blocks receptor signaling inhibits these changes and metastasis. Because VEGFR-3 is also essential for the early blood vessel development in embryos and is up-regulated in tumor angiogenesis, we wanted to determine if an antibody targeting the receptor that interferes with VEGFR-3 ligand binding can inhibit primary tumor growth. Our results show that antibody interference with VEGFR-3 function can inhibit the growth of several human tumor xenografts in immunocompromised mice. Immunohistochemical analysis showed that the blood vessel density of anti-VEGFR-3-treated tumors was significantly decreased and hypoxic and necrotic tumor tissue was increased when compared with tumors treated with control antibody, indicating that blocking of the VEGFR-3 pathway inhibits angiogenesis in these tumors. As expected, the anti-VEGFR-3-treated tumors also lacked lymphatic vessels. These results suggest that the VEGFR-3 pathway contributes to tumor angiogenesis and that effective inhibition of tumor progression may require the inhibition of multiple angiogenic targets.
    Original languageEnglish
    JournalCancer Research
    Issue number2
    Pages (from-to)593-599
    Number of pages7
    Publication statusPublished - 2007
    MoE publication typeA1 Journal article-refereed

    Cite this