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

Research output: Contribution to journalArticle

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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 Miatrigel, 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.

Original languageEnglish
Pages (from-to)172-179
Number of pages8
JournalBiology of Reproduction
Volume73
Issue number1
DOIs
Publication statusPublished - Jul 1 2005

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Trophoblasts
Integrins
Vascular Endothelial Growth Factor A
Tumor Necrosis Factor-alpha
Apoptosis
Cell Line
Extracellular Matrix
Cell Survival
Endothelial Cells
Protein Subunits
Human Development
Arteries
Pregnancy
Antibodies

All Science Journal Classification (ASJC) codes

  • Reproductive Medicine
  • Cell Biology

Cite this

Tumor necrosis factor and vascular endothelial growth factor induce endothelial integrin repertories, regulating endovascular differentiation and apoptosis in a human extravillous trophoblast cell line. / Fukushima, Kotaro; Miyamoto, Shingo; Tsukimori, Kiyomi; Kobayashi, Hiroaki; Seki, Hiroyuki; Takeda, Satoru; Kensuke, Egashira; Ohtani, Kishio; Shibuya, Masabumi; Nakano, Hitoo.

In: Biology of Reproduction, Vol. 73, No. 1, 01.07.2005, p. 172-179.

Research output: Contribution to journalArticle

Fukushima, Kotaro ; Miyamoto, Shingo ; Tsukimori, Kiyomi ; Kobayashi, Hiroaki ; Seki, Hiroyuki ; Takeda, Satoru ; Kensuke, Egashira ; Ohtani, Kishio ; Shibuya, Masabumi ; Nakano, Hitoo. / Tumor necrosis factor and vascular endothelial growth factor induce endothelial integrin repertories, regulating endovascular differentiation and apoptosis in a human extravillous trophoblast cell line. In: Biology of Reproduction. 2005 ; Vol. 73, No. 1. pp. 172-179.
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