Interleukin-6 induces vascular endothelial growth factor expression and promotes angiogenesis through apoptosis signal-regulating kinase 1 in human osteosarcoma

Huey En Tzeng, Chun Hao Tsai, Zi Ling Chang, Chen Ming Su, Shih Wei Wang, Wen Li Hwang, Chih Hsin Tang

Research output: Contribution to journalArticle

66 Citations (Scopus)

Abstract

Osteosarcoma is characterized by a high malignant and metastatic potential. Angiogenesis is essential for the caner metastasis. Interleukin-6 (IL-6) is a multifunctional cytokine that is associated with the disease status and outcomes of cancers. However, the relationship between IL-6 and vascular endothelial growth factor (VEGF) expression in human osteosarcoma is mostly unknown. Here we found that the IL-6 and VEGF expression was correlated with tumor stage and significantly higher than that in normal bone. Incubation of osteosarcoma cells with IL-6 increased VEGF mRNA and protein expression. Pretreatment of cells with IL-6R antibody reduced IL-6-mediated VEGF production. The apoptosis signal-regulating kinase 1 (ASK1)/p38/AP-1 pathway was activated after IL-6 treatment, and IL-6-induced VEGF expression was abolished by the specific inhibitor and siRNA of ASK1, p38, and AP-1 cascades. Importantly, knockdown IL-6 reduced VEGF expression and abolished osteosarcoma conditional medium-mediated angiogenesis. Taken together, these results indicate that IL-6 occurs through ASK1 and p38, which in turn activates AP-1, resulting in the activations of VEGF expression and contributing the angiogenesis of human osteosarcoma cells.

Original languageEnglish
Pages (from-to)531-540
Number of pages10
JournalBiochemical Pharmacology
Volume85
Issue number4
DOIs
Publication statusPublished - Feb 15 2013
Externally publishedYes

Fingerprint

MAP Kinase Kinase Kinase 5
Osteosarcoma
Vascular Endothelial Growth Factor A
Interleukin-6
Transcription Factor AP-1
human MAP3K5 protein
Small Interfering RNA
Tumors
Neoplasms
Bone
Chemical activation
Cells

Keywords

  • Angiogenesis
  • ASK1
  • IL-6
  • Osteosarcoma
  • VEGF

ASJC Scopus subject areas

  • Pharmacology
  • Biochemistry

Cite this

Interleukin-6 induces vascular endothelial growth factor expression and promotes angiogenesis through apoptosis signal-regulating kinase 1 in human osteosarcoma. / Tzeng, Huey En; Tsai, Chun Hao; Chang, Zi Ling; Su, Chen Ming; Wang, Shih Wei; Hwang, Wen Li; Tang, Chih Hsin.

In: Biochemical Pharmacology, Vol. 85, No. 4, 15.02.2013, p. 531-540.

Research output: Contribution to journalArticle

Tzeng, Huey En ; Tsai, Chun Hao ; Chang, Zi Ling ; Su, Chen Ming ; Wang, Shih Wei ; Hwang, Wen Li ; Tang, Chih Hsin. / Interleukin-6 induces vascular endothelial growth factor expression and promotes angiogenesis through apoptosis signal-regulating kinase 1 in human osteosarcoma. In: Biochemical Pharmacology. 2013 ; Vol. 85, No. 4. pp. 531-540.
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