WISP-1 positively regulates angiogenesis by controlling VEGF-A expression in human osteosarcoma

Hsiao Chi Tsai, Huey En Tzeng, Chun Yin Huang, Yuan Li Huang, Chun Hao Tsai, Shih Wei Wang, Po Chuan Wang, An Chen Chang, Yi Chin Fong, Chih Hsin Tang

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

In recent years, much research has focused on the role of angiogenesis in osteosarcoma, which occurs predominantly in adolescents and young adults. The vascular endothelial growth factor-A (VEGF-A) pathway is the key regulator of angiogenesis and in osteosarcoma. VEGF-A expression has been recognized as a prognostic marker in angiogenesis. Aberrant WNT1-inducible signaling pathway protein-1 (WISP-1) expression is associated with various cancers. However, the function of WISP-1 in osteosarcoma angiogenesis is poorly understood. We demonstrate a positive correlation between WISP-1 and VEGF-A expression in human osteosarcoma. Moreover, we show that WISP-1 promotes VEGF-A expression in human osteosarcoma cells, subsequently inducing human endothelial progenitor cell (EPC) migration and tube formation. The focal adhesion kinase (FAK), Jun amino-terminal kinase (JNK), and hypoxia-inducible factor (HIF)-1α signaling pathways were activated after WISP-1 stimulation, while FAK, JNK, and HIF-1α inhibitors or small interfering RNA (siRNA) abolished WISP-1-induced VEGF-A expression and angiogenesis. In vitro and in vivo studies revealed down-regulation of microRNA-381 (miR-381) in WISP-1-induced VEGF-A expression and angiogenesis. Our findings reveal that WISP-1 enhances VEGF-A expression and angiogenesis through the FAK/JNK/HIF-1α signaling pathways, as well as via down-regulation of miR-381 expression. WISP-1 may be a promising target in osteosarcoma angiogenesis.

Original languageEnglish
Article numbere2750
JournalCell Death and Disease
Volume8
Issue number4
DOIs
Publication statusPublished - Apr 13 2017
Externally publishedYes

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Osteosarcoma
Vascular Endothelial Growth Factor A
Focal Adhesion Protein-Tyrosine Kinases
MAP Kinase Kinase 4
Hypoxia-Inducible Factor 1
Proteins
MicroRNAs
Down-Regulation
Small Interfering RNA
Cell Movement
Young Adult
Research

ASJC Scopus subject areas

  • Immunology
  • Cellular and Molecular Neuroscience
  • Cell Biology
  • Cancer Research

Cite this

WISP-1 positively regulates angiogenesis by controlling VEGF-A expression in human osteosarcoma. / Tsai, Hsiao Chi; Tzeng, Huey En; Huang, Chun Yin; Huang, Yuan Li; Tsai, Chun Hao; Wang, Shih Wei; Wang, Po Chuan; Chang, An Chen; Fong, Yi Chin; Tang, Chih Hsin.

In: Cell Death and Disease, Vol. 8, No. 4, e2750, 13.04.2017.

Research output: Contribution to journalArticle

Tsai, HC, Tzeng, HE, Huang, CY, Huang, YL, Tsai, CH, Wang, SW, Wang, PC, Chang, AC, Fong, YC & Tang, CH 2017, 'WISP-1 positively regulates angiogenesis by controlling VEGF-A expression in human osteosarcoma', Cell Death and Disease, vol. 8, no. 4, e2750. https://doi.org/10.1038/cddis.2016.421
Tsai, Hsiao Chi ; Tzeng, Huey En ; Huang, Chun Yin ; Huang, Yuan Li ; Tsai, Chun Hao ; Wang, Shih Wei ; Wang, Po Chuan ; Chang, An Chen ; Fong, Yi Chin ; Tang, Chih Hsin. / WISP-1 positively regulates angiogenesis by controlling VEGF-A expression in human osteosarcoma. In: Cell Death and Disease. 2017 ; Vol. 8, No. 4.
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AB - In recent years, much research has focused on the role of angiogenesis in osteosarcoma, which occurs predominantly in adolescents and young adults. The vascular endothelial growth factor-A (VEGF-A) pathway is the key regulator of angiogenesis and in osteosarcoma. VEGF-A expression has been recognized as a prognostic marker in angiogenesis. Aberrant WNT1-inducible signaling pathway protein-1 (WISP-1) expression is associated with various cancers. However, the function of WISP-1 in osteosarcoma angiogenesis is poorly understood. We demonstrate a positive correlation between WISP-1 and VEGF-A expression in human osteosarcoma. Moreover, we show that WISP-1 promotes VEGF-A expression in human osteosarcoma cells, subsequently inducing human endothelial progenitor cell (EPC) migration and tube formation. The focal adhesion kinase (FAK), Jun amino-terminal kinase (JNK), and hypoxia-inducible factor (HIF)-1α signaling pathways were activated after WISP-1 stimulation, while FAK, JNK, and HIF-1α inhibitors or small interfering RNA (siRNA) abolished WISP-1-induced VEGF-A expression and angiogenesis. In vitro and in vivo studies revealed down-regulation of microRNA-381 (miR-381) in WISP-1-induced VEGF-A expression and angiogenesis. Our findings reveal that WISP-1 enhances VEGF-A expression and angiogenesis through the FAK/JNK/HIF-1α signaling pathways, as well as via down-regulation of miR-381 expression. WISP-1 may be a promising target in osteosarcoma angiogenesis.

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