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

Journal article

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.

Authors: Mandriota, S; Jussila, L; Jeltsch, M; Compagni, A; Baetens, D

• Publication status: Published
• Journal: EMBO journal
• Volume: 20
• Issue: 4
• Pages: 672-682
• Publication date: 2001-02-01
• DOI: 10.1093/emboj/20.4.672
• EISSN: 1460-2075
• ISSN: 0261-4189
• Language: English
• Keywords: Vascular Endothelial Growth Factor C; Endothelial Growth Factors; DNA, Complementary; Mice, Transgenic; Lymphatic System; Humans; Mice; Pancreas; Animals; Immunohistochemistry; Neoplasm Metastasis