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Oncodevelopmental -Fetoprotein Acts as a Selective Proangiogenic Factor on Endothelial Cell from the Fetomaternal Unit

Departments of Obstetrics and Gynecology (O.D.L., J.E., J.R., N.B., F.H., M.Z.) and Biochemistry (O.D.L., K.T.P.), Justus-Liebig-University, D-35385 Giessen, Germany; and Department of Vascular Biology and Angiogenesis Research (T.K.), Tumor Biology Center at the University of Freiburg, D-79106 Freiburg, Germany

Address all correspondence and requests for reprints to: Marek Zygmunt, M.D., Ph.D., Department of Obsterics and Gynecology, University of Giessen, Klinikstr. 32, D-35385 Giessen, Germany. E-mail: marek.zygmunt{at}gyn.med.uni-giessen.de.

The molecular coordination between angiogenesis and vascular remodeling is a critical step for the development of a functional vasculature in the placenta and the uterus during pregnancy. The oncodevelopmental albumin homolog -fetoprotein (AFP) is mainly synthesized in the developing fetus, and its expression has been found to be associated with highly vascularized tumors in the adult. In this study, we investigated the angiogenic activity of AFP and its possible role in the fetomaternal unit. Immunohistochemical studies revealed that the AFP-binding protein(s) is expressed in blood vessels of chorionic villi from placentae of the second and the third but not of the first trimester during pregnancy. At low concentrations, AFP directly stimulates or enhances, respectively, vascular endothelial growth factor-induced proliferation and sprout formation of endothelial cells isolated from the placenta and the uterus possibly by a MAPK-dependent pathway. Furthermore, AFP enhances blood vessel formation in a chick chorioallantoic membrane assay in vivo. Interestingly, AFP has no proliferative or migratory effects on endothelial cells isolated from the umbilical vein in the absence of vascular endothelial growth factor. These data indicate that AFP may act as a specific proangiogenic factor of endothelial cells within the fetomaternal unit during advanced stages in pregnancy.

Results from this work were presented at the Annual Meeting of the Society of Gynecologic Investigation, Los Angeles, CA, 2002.

This work was supported by a grant from the DFG-German Research Council (Zy 19/3-1, Bonn, Germany).

Abbreviations: AFP, -Fetoprotein; AFPBP, AFP-binding protein; bFGF, basic fibroblast growth factor; CAM, chick chorioallantoic membrane; FCS, fetal calf serum; HPEC, human placental microvascular endothelial cell; HSA, human serum albumin; HUVEC, human umbilical cord vein endothelial cell; mAb, monoclonal antibody; TBS, Tris-buffered saline; UMVEC, uterine microvascular endothelial cell; VEGF, vascular endothelial cell growth factor.

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