Journal
BLOOD
Volume 112, Issue 6, Pages 2318-2326Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2008-05-156331
Keywords
-
Categories
Funding
- National Institutes of Health [CA69184, CA86410]
- Swiss National Fund [3100A0108207]
- Austrian Science Foundation [S9408-B11]
- Cancer League Zurich
- Commission of the European Communities [LSHC-CT-2005-518178]
Ask authors/readers for more resources
Lymphatic vessel growth and activation, mediated by vascular endothelial growth factor (VEGF)-C and/or VEGF-A, have important roles in metastasis and in chronic inflammation. We aimed to comprehensively identify downstream molecular targets induced by VEGF-A or VEGF-C in lymphatic endothelium by analyzing the time-series transcriptional profile of treated human dermal lymphatic endothelial cells (LECs). We identified a number of genes, many not previously known to be involved in lymphangiogenesis, that were characterized either as early response genes, transiently induced genes, or progressively induced genes. Endothelial-specific molecule-1 (ESM-1) was one of the genes that were most potently induced by both VEGF-A and VEGF-C. Whereas ESM-1 induction by VEGF-A was mainly dependent on activation of VEGFR-2, VEGF-C-mediated induction depended on the activity of both VEGFR-2 and VEGFR-3. Incubation of LECs with ESM-1 increased the stimulatory effects of both VEGF-A and VEGF-C on LEC proliferation and migration, whereas ESM-1 alone had no effect. Importantly, VEGF-A (or VEGF-C) induction of LEC proliferation and migration were significantly inhibited by siRNA-mediated silencing of ESM-1 in vitro and in vivo. These studies reveal ESM-1 as a novel mediator of lymphangiogenesis and as a potential target for the inhibition of pathologic lymphatic vessel activation.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available