36 37

Dickkopf-1 induces angiogenesis via VEGF receptor 2 regulation independent of the Wnt signaling pathway

Authors
 Sung Hoon Choi  ;  Hyemi Kim  ;  Hyun Gyu Lee  ;  Beom Kyung Kim  ;  Jun Yong Park  ;  Do Young Kim  ;  Sang Hoon Ahn  ;  Kwang-Hyub Han  ;  Seung Up Kim 
Citation
 Oncotarget, Vol.8(35) : 58974-58984, 2017 
Journal Title
 Oncotarget 
Issue Date
2017
Keywords
HUVEC ; Hepatocellular carcinoma ; angiogenesis ; dickkopf-1 ; vascular endothelial growth factor receptor
Abstract
Tumor angiogenesis is essential for invasive tumor growth and metastasis. Dickkopf-1 (DKK-1), an antagonist of Wnt signaling, participates in tumor development and progression. We evaluated whether DKK-1 stimulation induces angiogenesis and the endothelial-mesenchymal transition (EnMT). Human umbilical vein endothelial cells (HUVECs) were stimulated with recombinant DKK-1 (rDDK-1) or conditioned medium from a culture of DKK-1-transfected 293 cells. Following stimulation, the expression levels of angiogenesis-related factors and EnMT related markers were determined by immunoblot assays. In addition, the effects of exogenous DKK-1 on angiogenesis and EnMT were assessed by tube-formation, cell invasion, and wound-healing assays. Human hepatoma cells, such as Hep3B and Huh-7, showed high levels of DKK-1 expression, whereas 293 cells and HUVECs showed little or no DKK-1 expression. Increased endothelial cell tube formation and invasiveness were observed in HUVECs treated with concentrated conditioned medium from DKK-1-overexpressing 293 cells or rDKK-1. DKK-1-stimulated HUVECs also exhibited increased motility in wound-healing assays. Furthermore, the expression levels of angiogenesis-related factors, including vascular endothelial growth factor receptor 2 and vascular endothelial-cadherin, were increased in DKK-1-stimulated HUVECs. The expression of EnMT markers, such as vimentin and Twist, was also increased in DKK-1-stimulated HUVECs. However, no significant change in β-catenin or GSK3β expression was observed. Our in vitro data suggest that DKK-1 can enhance angiogenesis and EnMT by HUVECs independent of the Wnt signaling pathway. Modulation of DKK-1 expression may facilitate development of novel strategies to control tumor angiogenesis and metastasis.
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/161109
Files in This Item:
T201704076.pdf Download
DOI
10.18632/oncotarget.19769
Appears in Collections:
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실)
Yonsei Authors
김도영(Kim, Do Young)
김범경(Kim, Beom Kyung) ORCID logo https://orcid.org/0000-0002-5363-2496
김승업(Kim, Seung Up)
박준용(Park, Jun Yong) ORCID logo https://orcid.org/0000-0001-6324-2224
안상훈(Ahn, Sang Hoon)
한광협(Han, Kwang Hyup)
Export
RIS (EndNote)
XLS (Excel)
XML
사서에게 알리기
  feedback

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse