Journal
PLOS ONE
Volume 5, Issue 11, Pages -Publisher
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0014109
Keywords
-
Categories
Funding
- Swedish Cancer Society
- Karolinska Institutet Cancer network
- Swedish Childhood Cancer Foundation
- Jeansson's Foundation
- Swedish Research Council
- EU [LSHG-CT-2004-503573]
- National Centre of Competence in Research (NCCR) Molecular Oncology of the Swiss National Science Foundation
- Swiss Cancer League
- Novo Nordisk Foundation
- Dr. Peter Wallenbergs Foundation for Economics and Technology
- Solderberg's Foundation
- Karolinska Institutet
Ask authors/readers for more resources
Background: The family of vascular endothelial growth factors (VEGF) contains key regulators of blood and lymph vessel development, including VEGF-A, -B, -C, -D, and placental growth factor. The role of VEGF-B during physiological or pathological angiogenesis has not yet been conclusively delineated. Herein, we investigate the function of VEGF-B by the generation of mouse models of cancer with transgenic expression of VEGF-B or homozygous deletion of Vegfb. Methodology/Principal Findings: Ectopic expression of VEGF-B in the insulin-producing beta-cells of the pancreas did not alter the abundance or architecture of the islets of Langerhans. The vasculature from transgenic mice exhibited a dilated morphology, but was of similar density as that of wildtype mice. Unexpectedly, we found that transgenic expression of VEGF-B in the RIP1-Tag2 mouse model of pancreatic neuroendocrine tumorigenesis retarded tumor growth. Conversely, RIP1-Tag2 mice deficient for Vegfb presented with larger tumors. No differences in vascular density, perfusion or immune cell infiltration upon altered Vegfb gene dosage were noted. However, VEGF-B acted to increase blood vessel diameter both in normal pancreatic islets and in RIP1-Tag2 tumors. Conclusions/Significance: Taken together, our results illustrate the differences in biological function between members of the VEGF family, and highlight the necessity of in-depth functional studies of VEGF-B to fully understand the effects of VEGFR-1 inhibitors currently used in the clinic.
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