HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 73/1/172    most recent biolreprod.104.039479v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Fukushima, K. Articles by Nakano, H. Search for Related Content PubMed PubMed Citation Articles by Fukushima, K. Articles by Nakano, H. Agricola Articles by Fukushima, K. Articles by Nakano, H.

Tumor Necrosis Factor and Vascular Endothelial Growth Factor Induce Endothelial Integrin Repertories, Regulating Endovascular Differentiation and Apoptosis in a Human Extravillous Trophoblast Cell Line¹

Departments of Obstetrics and Gynecology,³ Cardiovascular Medicine,⁴ Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, JapanDepartment of Obstetrics and Gynecology,⁵ Saitama Medical Center, Saitama Medical School, Saitama 350-8550, JapanDivision of Genetics,⁶ Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan

Angiogenesis is crucial in human development. Extravillous trophoblast (EVT) cells mimic endothelial cells in angiogenesis during endovascular differentiation, inducing a remodeling of spiral arteries that increases blood flow toward the intravillous space. We have previously shown that tumor necrosis factor (TNF) alpha regulates expression of ITGA6 and ITGA1, which are involved in cell survival, in the human EVT cell line TCL1. To further investigate endovascular differentiation, we examined the effects of vascular endothelial growth factor (VEGF), TNF, and extracellular matrix (ECM) on TCL1 cells. Seeded on Matrigel, TCL1 cells show tube-like formation that specifically recalls morphological changes in endothelial cells. Anti-ITGAV/ITGB3 antibodies significantly reduced the size of the capillary network (P < 0.05) on Matrigel and also suppressed TNF-induced apoptosis (P < 0.05) in TCL1 cells. VEGF induced expression of ITGAV/ITGB3 subunits and protein aggregation, as in the case of TNF, which in turn, induces synthesis of VEGF in TCL1 cells. Soluble FLT1 suppressed these activities in TCL1 cells, indicating that signals involving VEGF axis are essential for endovascular differentiation. These results suggest that TNF, VEGF, and ECM collaboratively regulate EVT behavior, including cell survival and endovascular differentiation, through integrin signaling during establishment and maintenance of successful human pregnancies.

cytokines, early development, placenta, pregnancy, trophoblast

² Correspondence: Kotaro Fukushima, Department of Obstetrics and Gynecology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. FAX: 81 92 642 5414; kfuku{at}gynob.med.kyushu-u.ac.jp

This article has been cited by other articles:

				T. W. Bonagura, G. J. Pepe, A. C. Enders, and E. D. Albrecht Suppression of Extravillous Trophoblast Vascular Endothelial Growth Factor Expression and Uterine Spiral Artery Invasion by Estrogen during Early Baboon Pregnancy Endocrinology, October 1, 2008; 149(10): 5078 - 5087. [Abstract] [Full Text] [PDF]

				M. Kerber, Y. Reiss, A. Wickersheim, M. Jugold, F. Kiessling, M. Heil, V. Tchaikovski, J. Waltenberger, M. Shibuya, K. H. Plate, et al. Flt-1 Signaling in Macrophages Promotes Glioma Growth In vivo Cancer Res., September 15, 2008; 68(18): 7342 - 7351. [Abstract] [Full Text] [PDF]