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

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 A Webster, Wei Li

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

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 1/2(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.

Original languageEnglish (US)
Article numbere0127904
JournalPLoS One
Volume10
Issue number5
DOIs
StatePublished - May 21 2015

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Angiogenesis Inducing Agents
hepatoma
growth factors
Endothelial cells
Assays
Human Umbilical Vein Endothelial Cells
Ligands
assays
Endothelial Cells
Proteins
Mitogen-Activated Protein Kinase 3
proteins
Mitogen-Activated Protein Kinase 1
endothelial cells
Nerve Growth Factors
DNA Sequence Analysis
Bacteriophages
Wound Healing
Cornea
Open Reading Frames

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

LeBlanc, M. E., Wang, W., Caberoy, N. B., Chen, X., Guo, F., Alvarado, G., ... Li, W. (2015). Hepatoma-derived growth factor-related protein-3 is a novel angiogenic factor. PLoS One, 10(5), [e0127904]. https://doi.org/10.1371/journal.pone.0127904

Hepatoma-derived growth factor-related protein-3 is a novel angiogenic factor. / LeBlanc, Michelle E.; Wang, Weiwen; Caberoy, Nora B.; Chen, Xiuping; Guo, Feiye; Alvarado, Gabriela; Shen, Chen; Wang, Feng; Wang, Hui; Chen, Rui; Liu, Zhao-Jun; Webster, Keith A; Li, Wei.

In: PLoS One, Vol. 10, No. 5, e0127904, 21.05.2015.

Research output: Contribution to journalArticle

LeBlanc, ME, Wang, W, Caberoy, NB, Chen, X, Guo, F, Alvarado, G, Shen, C, Wang, F, Wang, H, Chen, R, Liu, Z-J, Webster, KA & Li, W 2015, 'Hepatoma-derived growth factor-related protein-3 is a novel angiogenic factor', PLoS One, vol. 10, no. 5, e0127904. https://doi.org/10.1371/journal.pone.0127904
LeBlanc ME, Wang W, Caberoy NB, Chen X, Guo F, Alvarado G et al. Hepatoma-derived growth factor-related protein-3 is a novel angiogenic factor. PLoS One. 2015 May 21;10(5). e0127904. https://doi.org/10.1371/journal.pone.0127904
LeBlanc, Michelle E. ; Wang, Weiwen ; Caberoy, Nora B. ; Chen, Xiuping ; Guo, Feiye ; Alvarado, Gabriela ; Shen, Chen ; Wang, Feng ; Wang, Hui ; Chen, Rui ; Liu, Zhao-Jun ; Webster, Keith A ; Li, Wei. / Hepatoma-derived growth factor-related protein-3 is a novel angiogenic factor. In: PLoS One. 2015 ; Vol. 10, No. 5.
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