Hepatoma-derived growth factor-related protein-3 is a novel angiogenic factor.

Hepatoma-derived growth factor-related protein-3 (Hdgfrp3 or HRP-3) was recently reported as a neurotrophic factor and is upregulated in hepatocellular carcinoma to promote cancer cell survival. Here we identified HRP-3 as a new endothelial ligand and characterized its in vitro and in vivo functiona...

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Main Authors: Michelle E LeBlanc, Weiwen Wang, Nora B Caberoy, Xiuping Chen, Feiye Guo, Gabriela Alvarado, Chen Shen, Feng Wang, Hui Wang, Rui Chen, Zhao-Jun Liu, Keith Webster, Wei Li
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2015-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC4440747?pdf=render
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author Michelle E LeBlanc
Weiwen Wang
Nora B Caberoy
Xiuping Chen
Feiye Guo
Gabriela Alvarado
Chen Shen
Feng Wang
Hui Wang
Rui Chen
Zhao-Jun Liu
Keith Webster
Wei Li
author_facet Michelle E LeBlanc
Weiwen Wang
Nora B Caberoy
Xiuping Chen
Feiye Guo
Gabriela Alvarado
Chen Shen
Feng Wang
Hui Wang
Rui Chen
Zhao-Jun Liu
Keith Webster
Wei Li
author_sort Michelle E LeBlanc
collection DOAJ
description Hepatoma-derived growth factor-related protein-3 (Hdgfrp3 or HRP-3) was recently reported as a neurotrophic factor and is upregulated in hepatocellular carcinoma to promote cancer cell survival. Here we identified HRP-3 as a new endothelial ligand and characterized its in vitro and in vivo functional roles and molecular signaling. We combined open reading frame phage display with multi-round in vivo binding selection to enrich retinal endothelial ligands, which were systematically identified by next generation DNA sequencing. One of the identified endothelial ligands was HRP-3. HRP-3 expression in the retina and brain was characterized by Western blot and immunohistochemistry. Cell proliferation assay showed that HRP-3 stimulated the growth of human umbilical vein endothelial cells (HUVECs). HRP-3 induced tube formation of HUVECs in culture. Wound healing assay indicated that HRP-3 promoted endothelial cell migration. HRP-3 was further confirmed for its in vitro angiogenic activity by spheroid sprouting assay. HRP-3 extrinsically activated the extracellular-signal-regulated kinase ½ (ERK1/2) pathway in endothelial cells. The angiogenic activity of HRP-3 was independently verified by mouse cornea pocket assay. Furthermore, in vivo Matrigel plug assay corroborated HRP-3 activity to promote new blood vessel formation. These results demonstrated that HRP-3 is a novel angiogenic factor.
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spelling doaj.art-f10d966bddd14715910ec9504654a7422022-12-22T01:30:30ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01105e012790410.1371/journal.pone.0127904Hepatoma-derived growth factor-related protein-3 is a novel angiogenic factor.Michelle E LeBlancWeiwen WangNora B CaberoyXiuping ChenFeiye GuoGabriela AlvaradoChen ShenFeng WangHui WangRui ChenZhao-Jun LiuKeith WebsterWei LiHepatoma-derived growth factor-related protein-3 (Hdgfrp3 or HRP-3) was recently reported as a neurotrophic factor and is upregulated in hepatocellular carcinoma to promote cancer cell survival. Here we identified HRP-3 as a new endothelial ligand and characterized its in vitro and in vivo functional roles and molecular signaling. We combined open reading frame phage display with multi-round in vivo binding selection to enrich retinal endothelial ligands, which were systematically identified by next generation DNA sequencing. One of the identified endothelial ligands was HRP-3. HRP-3 expression in the retina and brain was characterized by Western blot and immunohistochemistry. Cell proliferation assay showed that HRP-3 stimulated the growth of human umbilical vein endothelial cells (HUVECs). HRP-3 induced tube formation of HUVECs in culture. Wound healing assay indicated that HRP-3 promoted endothelial cell migration. HRP-3 was further confirmed for its in vitro angiogenic activity by spheroid sprouting assay. HRP-3 extrinsically activated the extracellular-signal-regulated kinase ½ (ERK1/2) pathway in endothelial cells. The angiogenic activity of HRP-3 was independently verified by mouse cornea pocket assay. Furthermore, in vivo Matrigel plug assay corroborated HRP-3 activity to promote new blood vessel formation. These results demonstrated that HRP-3 is a novel angiogenic factor.http://europepmc.org/articles/PMC4440747?pdf=render
spellingShingle Michelle E LeBlanc
Weiwen Wang
Nora B Caberoy
Xiuping Chen
Feiye Guo
Gabriela Alvarado
Chen Shen
Feng Wang
Hui Wang
Rui Chen
Zhao-Jun Liu
Keith Webster
Wei Li
Hepatoma-derived growth factor-related protein-3 is a novel angiogenic factor.
PLoS ONE
title Hepatoma-derived growth factor-related protein-3 is a novel angiogenic factor.
title_full Hepatoma-derived growth factor-related protein-3 is a novel angiogenic factor.
title_fullStr Hepatoma-derived growth factor-related protein-3 is a novel angiogenic factor.
title_full_unstemmed Hepatoma-derived growth factor-related protein-3 is a novel angiogenic factor.
title_short Hepatoma-derived growth factor-related protein-3 is a novel angiogenic factor.
title_sort hepatoma derived growth factor related protein 3 is a novel angiogenic factor
url http://europepmc.org/articles/PMC4440747?pdf=render
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