Original Paper

Angiogenesis

, Volume 15, Issue 2, pp 229-242

First online:

Soluble HSPB1 regulates VEGF-mediated angiogenesis through their direct interaction

  • Yoon-Jin LeeAffiliated withDivision of Radiation Effects, Korea Institute of Radiological and Medical Sciences
  • , Hae-Jun LeeAffiliated withDivision of Radiation Effects, Korea Institute of Radiological and Medical Sciences
  • , Seo-hyun ChoiAffiliated withDivision of Radiation Effects, Korea Institute of Radiological and Medical SciencesSchool of Life Sciences and Biotechnology, Korea University
  • , Yeung Bae JinAffiliated withDivision of Radiation Effects, Korea Institute of Radiological and Medical Sciences
  • , Ho Jung AnAffiliated withDivision of Medical Oncology, Seoul St. Mary’s Hospital, The Catholic University
  • , Jin-Hyoung KangAffiliated withDivision of Medical Oncology, Seoul St. Mary’s Hospital, The Catholic University
  • , Sam S. YoonAffiliated withDepartment of Surgery, Massachusetts General Hospital and Harvard Medical School
  • , Yun-Sil LeeAffiliated withCollege of Pharmacy & Division of Life and Pharmaceutical Sciences, Ewha Womans University Email author 

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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)