02377nas a2200265   4500008004100000245014000041210006900181260001100250300001100261490000600272520152800278100001901806700002101825700002401846700002001870700002301890700002501913700002001938700002101958700001801979700001801997700002502015700002202040856004902062       2010                        eng d00aSuppressive effects of vascular endothelial growth factor-B on tumor growth in a mouse model of pancreatic neuroendocrine tumorigenesis0 aSuppressive effects of vascular endothelial growth factorB on tu  c2010//  ae141090 v53 aBACKGROUND: 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 β-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.1 aAlbrecht, Imke1 aKopfstein, Lucie1 aStrittmatter, Karin1 aSchomber, Tibor1 aFalkevall, Annelie1 aHagberg, Carolina, E1 aLorentz, Pascal1 aJeltsch, Michael1 aAlitalo, Kari1 aEriksson, Ulf1 aChristofori, Gerhard1 aPietras, Kristian  uhttp://view.ncbi.nlm.nih.gov/pubmed/21124841