Translator Disclaimer
1 July 2005 Tumor Necrosis Factor and Vascular Endothelial Growth Factor Induce Endothelial Integrin Repertories, Regulating Endovascular Differentiation and Apoptosis in a Human Extravillous Trophoblast Cell Line
Kotaro Fukushima, Shingo Miyamoto, Kiyomi Tsukimori, Hiroaki Kobayashi, Hiroyuki Seki, Satoru Takeda, Egashira Kensuke, Kishio Ohtani, Masabumi Shibuya, Hitoo Nakano
Author Affiliations +
Abstract

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.

Kotaro Fukushima, Shingo Miyamoto, Kiyomi Tsukimori, Hiroaki Kobayashi, Hiroyuki Seki, Satoru Takeda, Egashira Kensuke, Kishio Ohtani, Masabumi Shibuya, and Hitoo Nakano "Tumor Necrosis Factor and Vascular Endothelial Growth Factor Induce Endothelial Integrin Repertories, Regulating Endovascular Differentiation and Apoptosis in a Human Extravillous Trophoblast Cell Line," Biology of Reproduction 73(1), 172-179, (1 July 2005). https://doi.org/10.1095/biolreprod.104.039479
Received: 3 January 2005; Accepted: 1 March 2005; Published: 1 July 2005
JOURNAL ARTICLE
8 PAGES

This article is only available to subscribers.
It is not available for individual sale.
+ SAVE TO MY LIBRARY

SHARE
ARTICLE IMPACT
RIGHTS & PERMISSIONS
Get copyright permission
Back to Top