Clinical & Experimental Metastasis

, Volume 27, Issue 8, pp 601–609 | Cite as

Actin-sequestering protein, thymosin beta-4, is a novel hypoxia responsive regulator

  • Eun-Yi Moon
  • Yun-Sun Im
  • Yun-Kyoung Ryu
  • Joo-Hyun Kang
Research Paper

Abstract

Angiogenesis is induced by soluble factors such as vascular endothelial growth factor (VEGF) released from tumor cells in hypoxia. It enhances solid tumor growth and provides an ability to establish metastasis at peripheral sites by tumor cell migration. Thymosin beta-4 (TB4) is an actin-sequestering protein to control cytoskeletal reorganization. Here, we investigated whether angiogenesis and tumor metastasis are dependent on hypoxia conditioning-induced TB4 expression in B16F10 melanoma cells. TB4 expression in B16F10 cells was increased by hypoxia conditioning in a time-dependent manner. In addition, we found an increase of angiogenesis and HIF-1α expression in TB4-transgenic (Tg) mice as compared to wildtype mice. When wound healing assay was used to assess in vitro tumor cell migration, hypoxia conditioning for 1 h enhanced B16F10 cell migration. When TB4 expression in B16F10 cells was inhibited by the infection with small hairpin (sh) RNA of TB4 cloned in lentiviral vector, tumor cell migration was retarded. In addition, hypoxia conditioning-induced tumor cell migration was reduced by the infection of lentiviral shRNA of TB4. HIF-1α stabilization and the expression of VEGF isoform 165 and 121 in hypoxia were also reduced by the infection of lentiviral shRNA of TB4 in B16F10 cells. We also found an increase of tumor growth and lung metastasis count in TB4-Tg mice as compared to wildtype mice. Collectively, hypoxia conditioning induced tumor cell migration by TB4 expression-dependent HIF-1α stabilization. It suggests that TB4 could be a hypoxia responsive regulator to control tumor cell migration in angiogenesis and tumor metastasis.

Keywords

Thymosin beta-4 Hypoxia conditioning HIF-1α VEGF Tumor cell migration 

Abbreviations

TB4

Thymosin-beta-4

HIF-1α

Hypoxia inducible transcription factor 1 alpha

VEGF

Vascular endothelial growth factor

Tg

Transgenic

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Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  • Eun-Yi Moon
    • 1
  • Yun-Sun Im
    • 1
  • Yun-Kyoung Ryu
    • 1
  • Joo-Hyun Kang
    • 2
  1. 1.Department of Bioscience and BiotechnologySejong UniversitySeoulKorea
  2. 2.Molecular Imaging Research CenterKorea Institute of Radiological and Medical ScienceSeoulKorea

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