Angiogenesis

, Volume 15, Issue 2, pp 229–242

Soluble HSPB1 regulates VEGF-mediated angiogenesis through their direct interaction

  • Yoon-Jin Lee
  • Hae-Jun Lee
  • Seo-hyun Choi
  • Yeung Bae Jin
  • Ho Jung An
  • Jin-Hyoung Kang
  • Sam S. Yoon
  • Yun-Sil Lee
Original Paper

Abstract

Endothelial cell function is critical for angiogenic balance in both physiological and pathological conditions, such as wound healing and cancer, respectively. We report here that soluble heat shock protein beta-1 (HSPB1) is released primarily from endothelial cells (ECs), and plays a key role in regulating angiogenic balance via direct interaction with vascular endothelial growth factor (VEGF). VEGF-mediated phosphorylation of intracellular HSPB1 inhibited the secretion of HSPB1 and their binding activity in ECs. Interestingly, co-culture of tumor ECs with tumor cells decreased HSPB1 secretion from tumor ECs, suggesting that inhibition of HSPB1 secretion allows VEGF to promote angiogenesis. Additionally, neutralization of HSPB1 in a primary mouse sarcoma model promoted tumor growth, indicating the anti-angiogenic role of soluble HSPB1. Overexpression of HSPB1 by HSPB1 adenovirus was sufficient to suppress lung metastases of CT26 colon carcinoma in vivo, while neutralization of HSPB1 promoted in vivo wound healing. While VEGF-induced regulation of angiogenesis has been studied extensively, these findings illustrate the key contribution of HSPB1-VEGF interactions in the balance between physiological and pathological angiogenesis.

Keywords

Heat shock protein 25/27 (HSPB1) Angiogenic balance Vascular endothelial growth (VEGF) Endothelial cell (EC) 

Supplementary material

10456_2012_9255_MOESM1_ESM.doc (41 kb)
Supplementary material 1 (DOC 41 kb)
10456_2012_9255_MOESM2_ESM.pdf (524 kb)
Supplementary material 2 (PDF 523 kb)

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Copyright information

© Springer Science+Business Media B.V. 2012

Authors and Affiliations

  • Yoon-Jin Lee
    • 1
  • Hae-Jun Lee
    • 1
  • Seo-hyun Choi
    • 1
    • 2
  • Yeung Bae Jin
    • 1
  • Ho Jung An
    • 3
  • Jin-Hyoung Kang
    • 3
  • Sam S. Yoon
    • 4
  • Yun-Sil Lee
    • 5
  1. 1.Division of Radiation EffectsKorea Institute of Radiological and Medical SciencesSeoulKorea
  2. 2.School of Life Sciences and BiotechnologyKorea UniversitySeoulKorea
  3. 3.Division of Medical OncologySeoul St. Mary’s Hospital, The Catholic UniversitySeoulKorea
  4. 4.Department of SurgeryMassachusetts General Hospital and Harvard Medical SchoolBostonUSA
  5. 5.College of Pharmacy & Division of Life and Pharmaceutical Sciences, Ewha Womans UniversitySeoulKorea

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