IGF2 and IGF1R identified as novel tip cell genes in primary microvascular endothelial cell monolayers.

Details

Serval ID
serval:BIB_7F7291C8540F
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
IGF2 and IGF1R identified as novel tip cell genes in primary microvascular endothelial cell monolayers.
Journal
Angiogenesis
Author(s)
Dallinga M.G., Yetkin-Arik B., Kayser R.P., Vogels IMC, Nowak-Sliwinska P., Griffioen A.W., van Noorden CJF, Klaassen I., Schlingemann R.O.
ISSN
1573-7209 (Electronic)
ISSN-L
0969-6970
Publication state
Published
Issued date
11/2018
Peer-reviewed
Oui
Volume
21
Number
4
Pages
823-836
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Tip cells, the leading cells of angiogenic sprouts, were identified in cultures of human umbilical vein endothelial cells (HUVECs) by using CD34 as a marker. Here, we show that tip cells are also present in primary human microvascular endothelial cells (hMVECs), a more relevant endothelial cell type for angiogenesis. By means of flow cytometry, immunocytochemistry, and qPCR, it is shown that endothelial cell cultures contain a dynamic population of CD34 <sup>+</sup> cells with many hallmarks of tip cells, including filopodia-like extensions, elevated mRNA levels of known tip cell genes, and responsiveness to stimulation with VEGF and inhibition by DLL4. Furthermore, we demonstrate that our in vitro tip cell model can be exploited to investigate cellular and molecular mechanisms in tip cells and to discover novel targets for anti-angiogenesis therapy in patients. Small interfering RNA (siRNA) was used to knockdown gene expression of the known tip cell genes angiopoietin 2 (ANGPT2) and tyrosine kinase with immunoglobulin-like and EGF-like domains 1 (TIE1), which resulted in similar effects on tip cells and sprouting as compared to inhibition of tip cells in vivo. Finally, we identified two novel tip cell-specific genes in CD34 <sup>+</sup> tip cells in vitro: insulin-like growth factor 2 (IGF2) and IGF-1-receptor (IGF1R). Knockdown of these genes resulted in a significant decrease in the fraction of tip cells and in the extent of sprouting in vitro and in vivo. In conclusion, this study shows that by using our in vitro tip cell model, two novel essential tip cells genes are identified.
Keywords
Angiopoietin-2/genetics, Angiopoietin-2/metabolism, Animals, Chick Embryo, Gene Knockdown Techniques, Human Umbilical Vein Endothelial Cells/cytology, Human Umbilical Vein Endothelial Cells/metabolism, Humans, Insulin-Like Growth Factor II/genetics, Insulin-Like Growth Factor II/metabolism, Microvessels/cytology, Microvessels/metabolism, Receptor, TIE-1/genetics, Receptor, TIE-1/metabolism, Receptors, Somatomedin/genetics, Receptors, Somatomedin/metabolism, Zebrafish, Angiogenesis, CD34, Cultured cells, Endothelial cells, Endothelial growth factors, IGF2, Tip cells
Pubmed
Web of science
Open Access
Yes
Create date
29/06/2018 15:46
Last modification date
27/10/2019 6:11
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