Identification of an angiogenic mitogen selective for endocrine gland endothelium

Jennifer LeCouter, Joe Kowalski, Jessica Foster, Phil Hass, Zemin Zhang, Lisa Dillard-Telm, Gretchen Frantz, Linda Rangell, Leo DeGuzman, Gilbert-Andre Keller, Franklin Peale, Austin Gurney, Kenneth J. Hillan and Napoleone Ferrara ()
Additional contact information
Jennifer LeCouter: Department of Molecular Oncology
Joe Kowalski: Department of Molecular Oncology
Jessica Foster: Genentech Inc.
Phil Hass: Genentech Inc.
Zemin Zhang: Genentech Inc.
Lisa Dillard-Telm: Genentech Inc.
Gretchen Frantz: Genentech Inc.
Linda Rangell: Genentech Inc.
Leo DeGuzman: Department of Molecular Oncology
Gilbert-Andre Keller: Genentech Inc.
Franklin Peale: Genentech Inc.
Austin Gurney: Genentech Inc.
Kenneth J. Hillan: Genentech Inc.
Napoleone Ferrara: Department of Molecular Oncology

Nature, 2001, vol. 412, issue 6850, 877-884

Abstract: Abstract The known endothelial mitogens stimulate growth of vascular endothelial cells without regard to their tissue of origin. Here we report a growth factor that is expressed largely in one type of tissue and acts selectively on one type of endothelium. This molecule, called endocrine-gland-derived vascular endothelial growth factor (EG-VEGF), induced proliferation, migration and fenestration (the formation of membrane discontinuities) in capillary endothelial cells derived from endocrine glands. However, EG-VEGF had little or no effect on a variety of other endothelial and non-endothelial cell types tested. Similar to VEGF, EG-VEGF possesses a HIF-1 binding site, and its expression is induced by hypoxia. Both EG-VEGF and VEGF resulted in extensive angiogenesis and cyst formation when delivered in the ovary. However, unlike VEGF, EG-VEGF failed to promote angiogenesis in the cornea or skeletal muscle. Expression of human EG-VEGF messenger RNA is restricted to the steroidogenic glands, ovary, testis, adrenal and placenta and is often complementary to the expression of VEGF, suggesting that these molecules function in a coordinated manner. EG-VEGF is an example of a class of highly specific mitogens that act to regulate proliferation and differentiation of the vascular endothelium in a tissue-specific manner.

Date: 2001
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DOI: 10.1038/35091000

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