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Vascular endothelial growth factor-C-mediated lymphangiogenesis promotes tumour metastasis

Jussila, Lotta
Jeltsch, Michael
Compagni, Amelia
Prevo, Remko
Banerji, Suneale
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Published in EMBO journal. 2001, vol. 20, no. 4, p. 672-82
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 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.
Keywords AnimalsDNA, ComplementaryEndothelial Growth Factors/genetics/physiologyHumansImmunohistochemistryLymphatic System/growth & developmentMiceMice, TransgenicNeoplasm MetastasisPancreas/ultrastructureVascular Endothelial Growth Factor C
PMID: 11179212
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MANDRIOTA, Stefano Jacopo et al. Vascular endothelial growth factor-C-mediated lymphangiogenesis promotes tumour metastasis. In: EMBO journal, 2001, vol. 20, n° 4, p. 672-82. doi: 10.1093/emboj/20.4.672 https://archive-ouverte.unige.ch/unige:3862

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Deposited on : 2009-10-22

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