[HTML][HTML] Vascular endothelial growth factor‐C‐mediated lymphangiogenesis promotes tumour metastasis

SJ Mandriota, L Jussila, M Jeltsch, A Compagni… - The EMBO …, 2001 - embopress.org
SJ Mandriota, L Jussila, M Jeltsch, A Compagni, D Baetens, R Prevo, S Banerji, J Huarte…
The EMBO journal, 2001embopress.org
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 β‐cells …
Abstract
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 β‐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 β‐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 β‐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.
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