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.
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Acknowledgments
We thank Dr. Sandra Ryeom (University of Pennsylvania Medical School) for helpful discussions and Dr. Christiana DelloRusso for assistance editing the manuscript. This work was supported by the Nuclear Research and Development Program (Grant No. M2AMA006), Basic Science Research Program (Grant No. R1A4A002), and Mid-career Researcher Program (Grat No. 2011-0013364) of the National Research Foundation of Korea (NRF) funded by the Korean Ministry of Education, Science, and Technology (MEST).
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Lee, YJ., Lee, HJ., Choi, Sh. et al. Soluble HSPB1 regulates VEGF-mediated angiogenesis through their direct interaction. Angiogenesis 15, 229–242 (2012). https://doi.org/10.1007/s10456-012-9255-3
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DOI: https://doi.org/10.1007/s10456-012-9255-3