PARENT SESSION
MINISYMPOSIUM VI. Regulation of Angiogenesis in the Reproductive System.
11:00 AM-12:30 PM
Harborside E
Chair: Koos, Robert¹, ¹

(M17) EG-VEGF AND THE HYPOTHESIS OF TISSUE-SPECIFIC REGULATION OF ANGIOGENESIS.

Ferrara, Napoleone¹, LeCouter, Jennifer¹, Lin, Rui¹, ¹ Dept. Molecular Oncology. Genentech inc., So San Francico, CA

ABSTRACT- There is compelling evidence that certain families of endothelial cell-specific tyrosine kinases and their ligands (e.g. VEGFR/VEGF, Tie2/Ang) are essential for embryonic development and for angiogenesis in a wide variety of physiological and pathological circumstances. There is also evidence for a tissue-specific regulation of endothelial cell phenotype and, in some circumstances, growth. However, the molecular basis for this influence of the "microenvironment" on the vasculature is unknown. We recently identified EG-VEGF, an endothelial cell mitogen with a unique selectivity, essentially limited to endothelial cells derived from endocrine organs. Northern analysis shows that EG-VEGF expression is virtually restricted to steroidogenic tissues, with highest expression in ovary and testis, followed by adrenal cortex and placenta. In situ hybridization shows that EG-VEGF mRNA expression is localized to the steroid hormone-producing cells, i.e. Leydig cells of the testis and the specialized stroma in the ovary. A key feature of the capillary endothelium of steroidogenic tissues is the presence of fenestration, EG-VEGF induces fenestration in cultured ACE cells to an extent comparable to VEGF, and a combination of the two factors is synergistic. Recent evidence indicates that the EG-VEGF receptor(s) belongs to the family of GPCRs. In vivo experiments, using adenovirus-delivered EG-VEGF, demonstrated a strong angiogenic response in endocrine tissues such as ovary, testis and adrenal, but no apparent effect in the skeletal muscle and cornea. These findings indicate that EG-VEGF represents a novel type of endothelial cell-specific effector that acts in a tissue-specific manner to determine the phenotype and promote the growth of the resident endothelial cells. These findings also raise the possibility that additional organ-specific endothelial cell mitogens/regulators exist, which may have important pathophysiological and therapeutic implications.

KEY WORDS: Angiogenesis, Ovary , Testis , EG-VEGF