PURPOSE: Multiple endocrine neoplasia type 1 (MEN1) is defined clinically by the 
combined occurrence of multiple tumors, typically of the parathyroid glands, 
pancreatic islet cells, and anterior pituitary gland. A mouse model with a 
heterozygous deletion of the Men1 gene recapitulates the tumorigenesis of MEN1. 
We wished to determine the role of vascular endothelial growth factor (VEGF)-A 
in the vascularization and growth of MEN1-associated tumors, with an emphasis on 
pituitary adenomas.
EXPERIMENTAL DESIGN: To investigate whether tumor growth in Men1(+/-) mice is 
mediated by VEGF-A dependent angiogenesis, we carried out a monotherapy with the 
anti-VEGF-A monoclonal antibody (mAb) G6-31. We evaluated tumor growth by 
magnetic resonance imaging and assessed vascular density in tissue sections. We 
also measured hormone levels in the serum.
RESULTS: During the treatment with mAb G6-31, a significant inhibition of the 
pituitary adenoma growth was observed, leading to an increased mean tumor 
doubling-free survival compared with mice treated with a control antibody. 
Similarly, the growth of s.c. pituitary adenoma transplants was effectively 
inhibited by administration of anti-VEGF-A mAb. Serum prolactin was lowered by 
mAb G6-31 treatment but not by control antibody, potentially providing a new 
therapeutic approach for treating the hormonal excess in MEN1 patients. 
Additionally, the vascular density in pancreatic islet tumors was significantly 
reduced by the treatment.
CONCLUSIONS: These results suggest that VEGF-A blockade may represent a 
nonsurgical treatment for benign tumors of the endocrine system.