Distinct roles of vascular endothelial growth factor-D in lymphangiogenesis and metastasis

Kopfstein, Lucie; Veikkola, Tanja; Djonov, Valentin G; Baeriswyl, Vanessa; Schomber, Tibor; Strittmatter, Karin; Stacker, Steven A; Achen, Marc G; Alitalo, Kari; Christofori, Gerhard (2007). Distinct roles of vascular endothelial growth factor-D in lymphangiogenesis and metastasis. American journal of pathology, 170(4), pp. 1348-61. New York, N.Y.: Elsevier 10.2353/ajpath.2007.060835

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In many human carcinomas, expression of the lymphangiogenic factor vascular endothelial growth factor-D (VEGF-D) correlates with up-regulated lymphangiogenesis and regional lymph node metastasis. Here, we have used the Rip1Tag2 transgenic mouse model of pancreatic beta-cell carcinogenesis to investigate the functional role of VEGF-D in the induction of lymphangiogenesis and tumor progression. Expression of VEGF-D in beta cells of single-transgenic Rip1VEGF-D mice resulted in the formation of peri-insular lymphatic lacunae, often containing leukocyte accumulations and blood hemorrhages. When these mice were crossed to Rip1Tag2 mice, VEGF-D-expressing tumors also exhibited peritumoral lymphangiogenesis with lymphocyte accumulations and hemorrhages, and they frequently developed lymph node and lung metastases. Notably, tumor outgrowth and blood microvessel density were significantly reduced in VEGF-D-expressing tumors. Our results demonstrate that VEGF-D induces lymphangiogenesis, promotes metastasis to lymph nodes and lungs, and yet represses hemangiogenesis and tumor outgrowth. Because a comparable transgenic expression of vascular endothelial growth factor-C (VEGF-C) in Rip1Tag2 has been shown previously to provoke lymphangiogenesis and lymph node metastasis in the absence of any distant metastasis, leukocyte infiltration, or angiogenesis-suppressing effects, these results reveal further functional differences between VEGF-D and VEGF-C.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy

UniBE Contributor:

Djonov, Valentin

ISSN:

0002-9440

ISBN:

17392173

Publisher:

Elsevier

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:56

Last Modified:

04 May 2014 23:16

Publisher DOI:

10.2353/ajpath.2007.060835

PubMed ID:

17392173

Web of Science ID:

000245233000021

URI:

https://boris.unibe.ch/id/eprint/23711 (FactScience: 43548)

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