Premium
Vascular endothelial growth factor‐C‐mediated lymphangiogenesis promotes tumour metastasis
Author(s) -
Mandriota Stefano J.,
Jussila Lotta,
Jeltsch Michael,
Compagni Amelia,
Baetens Danielle,
Prevo Remko,
Banerji Suneale,
Huarte Joachim,
Montesano Roberto,
Jackson David G.,
Orci Lelio,
Alitalo Kari,
Christofori Gerhard,
Pepper Michael S.
Publication year - 2001
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/20.4.672
Subject(s) - lymphangiogenesis , biology , vascular endothelial growth factor c , lymphatic system , cancer research , metastasis , pancreas , pathology , lymph node , vascular endothelial growth factor , vascular endothelial growth factor a , cancer , immunology , endocrinology , medicine , vegf receptors , genetics
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.