GDNF secreted from adipose-derived stem cells stimulates VEGF-independent angiogenesis

Zhaohui Zhong, Huiying Gu, Jirun Peng, Wenzheng Wang, Brian H. Johnstone, Keith L. March, Martin Farlow, Yansheng Du

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Adipose tissue stroma contains a population of mesenchymal stem cells (MSC) promote new blood vessel formation and stabilization. These adipose-derived stem cells (ASC) promote de novo formation of vascular structures in vitro. We investigated the angiogenic factors secreted by ASC and discovered that glial-derived neurotrophic factor (GDNF) is a key mediator for endothelial cell network formation. It was found that both GDNF alone or present in ASC-conditioned medium (ASC-CM) stimulated capillary network formation by using human umbilical vein endothelial cells (HUVECs) and such an effect was totally independent of vascular endothelial growth factor (VEGF) activity. Additionally, we showed stimulation of capillary network formation by GDNF, but not VEGF, could be blocked by the Ret (rearranged during transfection) receptor antagonist RPI-1, a GDNF signaling inhibitor. Furthermore, GDNF were found to be overexpressed in cancer cells that were resistant to the anti-angiogenic treatment using the VEGF antibody. Cancer cells in the liver hepatocellular carcinoma (HCC), a non-nervous related cancer, highly overexpressed GDNF as compared to normal liver cells. Our data strongly suggest that, in addition to VEGF, GDNF secreted by ASC and HCC cells, may be another important factor promoting pathological neovascularization. Thus, GDNF may be a potential therapeutic target for HCC and obesity treatments.

Original languageEnglish (US)
Pages (from-to)36829-36841
Number of pages13
JournalOncotarget
Volume7
Issue number24
DOIs
StatePublished - 2016

Fingerprint

Nerve Growth Factors
Neuroglia
Vascular Endothelial Growth Factor A
Stem Cells
Hepatocellular Carcinoma
Blood Vessels
Pathologic Neovascularization
Neoplasms
Angiogenesis Inducing Agents
Liver
Human Umbilical Vein Endothelial Cells
Conditioned Culture Medium
Mesenchymal Stromal Cells
Transfection
Adipose Tissue
Endothelial Cells
Obesity
Antibodies
Population

Keywords

  • Angiogenesis
  • ASC-CM
  • GDNF
  • Hepatocellular carcinoma
  • VEGF

ASJC Scopus subject areas

  • Oncology

Cite this

Zhong, Z., Gu, H., Peng, J., Wang, W., Johnstone, B. H., March, K. L., ... Du, Y. (2016). GDNF secreted from adipose-derived stem cells stimulates VEGF-independent angiogenesis. Oncotarget, 7(24), 36829-36841. https://doi.org/10.18632/oncotarget.9208

GDNF secreted from adipose-derived stem cells stimulates VEGF-independent angiogenesis. / Zhong, Zhaohui; Gu, Huiying; Peng, Jirun; Wang, Wenzheng; Johnstone, Brian H.; March, Keith L.; Farlow, Martin; Du, Yansheng.

In: Oncotarget, Vol. 7, No. 24, 2016, p. 36829-36841.

Research output: Contribution to journalArticle

Zhong, Z, Gu, H, Peng, J, Wang, W, Johnstone, BH, March, KL, Farlow, M & Du, Y 2016, 'GDNF secreted from adipose-derived stem cells stimulates VEGF-independent angiogenesis', Oncotarget, vol. 7, no. 24, pp. 36829-36841. https://doi.org/10.18632/oncotarget.9208
Zhong, Zhaohui ; Gu, Huiying ; Peng, Jirun ; Wang, Wenzheng ; Johnstone, Brian H. ; March, Keith L. ; Farlow, Martin ; Du, Yansheng. / GDNF secreted from adipose-derived stem cells stimulates VEGF-independent angiogenesis. In: Oncotarget. 2016 ; Vol. 7, No. 24. pp. 36829-36841.
@article{ddacbe7311514ef6a93219cbd2f392d4,
title = "GDNF secreted from adipose-derived stem cells stimulates VEGF-independent angiogenesis",
abstract = "Adipose tissue stroma contains a population of mesenchymal stem cells (MSC) promote new blood vessel formation and stabilization. These adipose-derived stem cells (ASC) promote de novo formation of vascular structures in vitro. We investigated the angiogenic factors secreted by ASC and discovered that glial-derived neurotrophic factor (GDNF) is a key mediator for endothelial cell network formation. It was found that both GDNF alone or present in ASC-conditioned medium (ASC-CM) stimulated capillary network formation by using human umbilical vein endothelial cells (HUVECs) and such an effect was totally independent of vascular endothelial growth factor (VEGF) activity. Additionally, we showed stimulation of capillary network formation by GDNF, but not VEGF, could be blocked by the Ret (rearranged during transfection) receptor antagonist RPI-1, a GDNF signaling inhibitor. Furthermore, GDNF were found to be overexpressed in cancer cells that were resistant to the anti-angiogenic treatment using the VEGF antibody. Cancer cells in the liver hepatocellular carcinoma (HCC), a non-nervous related cancer, highly overexpressed GDNF as compared to normal liver cells. Our data strongly suggest that, in addition to VEGF, GDNF secreted by ASC and HCC cells, may be another important factor promoting pathological neovascularization. Thus, GDNF may be a potential therapeutic target for HCC and obesity treatments.",
keywords = "Angiogenesis, ASC-CM, GDNF, Hepatocellular carcinoma, VEGF",
author = "Zhaohui Zhong and Huiying Gu and Jirun Peng and Wenzheng Wang and Johnstone, {Brian H.} and March, {Keith L.} and Martin Farlow and Yansheng Du",
year = "2016",
doi = "10.18632/oncotarget.9208",
language = "English (US)",
volume = "7",
pages = "36829--36841",
journal = "Oncotarget",
issn = "1949-2553",
publisher = "Impact Journals",
number = "24",

}

TY - JOUR

T1 - GDNF secreted from adipose-derived stem cells stimulates VEGF-independent angiogenesis

AU - Zhong, Zhaohui

AU - Gu, Huiying

AU - Peng, Jirun

AU - Wang, Wenzheng

AU - Johnstone, Brian H.

AU - March, Keith L.

AU - Farlow, Martin

AU - Du, Yansheng

PY - 2016

Y1 - 2016

N2 - Adipose tissue stroma contains a population of mesenchymal stem cells (MSC) promote new blood vessel formation and stabilization. These adipose-derived stem cells (ASC) promote de novo formation of vascular structures in vitro. We investigated the angiogenic factors secreted by ASC and discovered that glial-derived neurotrophic factor (GDNF) is a key mediator for endothelial cell network formation. It was found that both GDNF alone or present in ASC-conditioned medium (ASC-CM) stimulated capillary network formation by using human umbilical vein endothelial cells (HUVECs) and such an effect was totally independent of vascular endothelial growth factor (VEGF) activity. Additionally, we showed stimulation of capillary network formation by GDNF, but not VEGF, could be blocked by the Ret (rearranged during transfection) receptor antagonist RPI-1, a GDNF signaling inhibitor. Furthermore, GDNF were found to be overexpressed in cancer cells that were resistant to the anti-angiogenic treatment using the VEGF antibody. Cancer cells in the liver hepatocellular carcinoma (HCC), a non-nervous related cancer, highly overexpressed GDNF as compared to normal liver cells. Our data strongly suggest that, in addition to VEGF, GDNF secreted by ASC and HCC cells, may be another important factor promoting pathological neovascularization. Thus, GDNF may be a potential therapeutic target for HCC and obesity treatments.

AB - Adipose tissue stroma contains a population of mesenchymal stem cells (MSC) promote new blood vessel formation and stabilization. These adipose-derived stem cells (ASC) promote de novo formation of vascular structures in vitro. We investigated the angiogenic factors secreted by ASC and discovered that glial-derived neurotrophic factor (GDNF) is a key mediator for endothelial cell network formation. It was found that both GDNF alone or present in ASC-conditioned medium (ASC-CM) stimulated capillary network formation by using human umbilical vein endothelial cells (HUVECs) and such an effect was totally independent of vascular endothelial growth factor (VEGF) activity. Additionally, we showed stimulation of capillary network formation by GDNF, but not VEGF, could be blocked by the Ret (rearranged during transfection) receptor antagonist RPI-1, a GDNF signaling inhibitor. Furthermore, GDNF were found to be overexpressed in cancer cells that were resistant to the anti-angiogenic treatment using the VEGF antibody. Cancer cells in the liver hepatocellular carcinoma (HCC), a non-nervous related cancer, highly overexpressed GDNF as compared to normal liver cells. Our data strongly suggest that, in addition to VEGF, GDNF secreted by ASC and HCC cells, may be another important factor promoting pathological neovascularization. Thus, GDNF may be a potential therapeutic target for HCC and obesity treatments.

KW - Angiogenesis

KW - ASC-CM

KW - GDNF

KW - Hepatocellular carcinoma

KW - VEGF

UR - http://www.scopus.com/inward/record.url?scp=84978066158&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84978066158&partnerID=8YFLogxK

U2 - 10.18632/oncotarget.9208

DO - 10.18632/oncotarget.9208

M3 - Article

C2 - 27167204

AN - SCOPUS:84978066158

VL - 7

SP - 36829

EP - 36841

JO - Oncotarget

JF - Oncotarget

SN - 1949-2553

IS - 24

ER -