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Vascular endothelial growth factor receptor 3 is involved in tumor angiogenesis and growth.
Laakkonen, Pirjo; Waltari, Marika; Holopainen, Tanja; Takahashi, Takashi; Pytowski, Bronislaw; Steiner, Philipp; Hicklin, Daniel; Persaud, Kris; Tonra, James R; Witte, Larry; Alitalo, Kari.
  • Laakkonen P; Molecular/Cancer Biology Research Program and Ludwig Institute for Cancer Research, Biomedicum Helsinki, Haartman Institute and Helsinki University Central Hospital, University of Helsinki, Finland.
Cancer Res ; 67(2): 593-9, 2007 Jan 15.
Article en En | MEDLINE | ID: mdl-17234768
ABSTRACT
Vascular endothelial growth factor receptor 3 (VEGFR-3) binds VEGF-C and VEGF-D and is essential for the development of the lymphatic vasculature. 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 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.
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Banco de datos: MEDLINE Asunto principal: Receptor 3 de Factores de Crecimiento Endotelial Vascular / Anticuerpos Monoclonales / Neoplasias Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Año: 2007 Tipo del documento: Article
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Banco de datos: MEDLINE Asunto principal: Receptor 3 de Factores de Crecimiento Endotelial Vascular / Anticuerpos Monoclonales / Neoplasias Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Año: 2007 Tipo del documento: Article