Community Research and Development Information Service - CORDIS

Soluble VEGFR3 to inhibit metastasis via the lymphatic system

The VEGFR-3 receptor tyrosine kinase is related to the VEGF receptors, but does not bind VEGF and its expression becomes restricted mainly to lymphatic endothelia during development. Partner 2 has found that homozygous VEGFR-3 targeted mice die around day 10 of embryonic development due to failure of cardiovascular development. He has also purified and cloned the VEGFR-3 ligand, VEGF-C. When overexpressed as a transgene in the RIP-Tag model of pancreatic beta-cell tumors, VEGF-C induced the growth of peritumoral lymphatic vessels and was associated with lymphatic metastasis. VEGF-C overexpression also led to lymphangiogenesis, intralymphatic tumor growth and lymph node metastasis in an orthotopic model of human breast carcinoma in immunoincompetent mice. Furthermore, soluble VEGFR-3, which blocks embryonic lymphangiogenesis, blocked these changes.

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UNIVERSITY OF HELSINKI
Haartmaninkatu 3
00014 HELSINKI
Finland
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