Vascular endothelial growth factor-C-mediated lymphangiogenesis promotes tumour metastasis.
EMBO J
; 20(4): 672-82, 2001 Feb 15.
Article
in En
| MEDLINE
| ID: mdl-11179212
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Endothelial Growth Factors
/
Lymphatic System
/
Neoplasm Metastasis
Limits:
Animals
/
Humans
Language:
En
Journal:
EMBO J
Year:
2001
Document type:
Article
Affiliation country:
Suiza