%0 Journal Article %J EMBO J %D 2001 %T Vascular endothelial growth factor-C-mediated lymphangiogenesis promotes tumour metastasis %A Mandriota, S J %A Jussila, L %A Jeltsch, M %A Compagni, A %A Baetens, D %A Prevo, R %A Banerji, S %A Huarte, J %A Montesano, R %A Jackson, D G %A Orci, L %A Alitalo, K %A Christofori, G %A Pepper, M S %X Metastasis is a frequent and lethal complication of cancer. Vascular endothelial growth factor-C (VEGF-C) is a recently described lymphangiogenic factor. Increased expression of VEGF-C in primary tumours correlates with dissemination of tumour cells to regional lymph nodes. However, a direct role for VEGF-C in tumour lymphangiogenesis and subsequent metastasis has yet to be demonstrated. Here we report the establishment of transgenic mice in which VEGF-C expression, driven by the rat insulin promoter (Rip), is targeted to beta-cells of the endocrine pancreas. In contrast to wild-type mice, which lack peri-insular lymphatics, RipVEGF-C transgenics develop an extensive network of lymphatics around the islets of Langerhans. These mice were crossed with Rip1Tag2 mice, which develop pancreatic beta-cell tumours that are neither lymphangiogenic nor metastatic. Double-transgenic mice formed tumours surrounded by well developed lymphatics, which frequently contained tumour cell masses of beta-cell origin. These mice frequently developed pancreatic lymph node metastases. Our findings demonstrate that VEGF-C-induced lymphangiogenesis mediates tumour cell dissemination and the formation of lymph node metastases. %B EMBO J %V 20 %P 672 - 82 %8 2001/Feb/ %G eng %U http://view.ncbi.nlm.nih.gov/pubmed/11179212 %N 4 %! The EMBO Journal