Inhibitor of differentiation 1 in U87MG glioblastoma cells promotes HUVEC sprouting through endothelin‑1

Choi,Sang-Hun; Park,Min Ji; Kim,Hyunggee

doi:10.3892/ol.2022.13533

Inhibitor of differentiation 1 in U87MG glioblastoma cells promotes HUVEC sprouting through endothelin‑1

Authors:
- Sang-Hun Choi
- Min Ji Park
- Hyunggee Kim
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Affiliations: Department of Biotechnology, College of Life Science and Biotechnology, Korea University, Seoul 02841, Republic of Korea
Published online on: September 27, 2022 https://doi.org/10.3892/ol.2022.13533
Article Number: 413
Copyright: © Choi et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Anti‑angiogenesis therapy, a promising remedy against tumor progression, is now widely used to treat numerous types of cancer. Since vascular endothelial growth factor (VEGF) is the most vital factor in angiogenesis, most anti‑angiogenesis drugs target the VEGF‑related pathway. However, in glioblastoma (GBM), the therapeutic strategy involving the inhibition of VEGF signaling is ineffective. The present study demonstrated that the potential angiogenic function of endothelin‑1 (EDN1) was upregulated by inhibitor of differentiation 1 (ID1) independent of VEGF during tumor angiogenesis. Anatomic structure transcriptomes of patients with GBM revealed that the expression levels of ID1 and EDN1 were specifically upregulated in the vascular‑related region. The aortic ring assay and endothelial sprouting assay demonstrated that EDN1 more potently promoted endothelial sprouting ability than VEGF. The activity of EDN1 was induced by endothelin receptor, which seemed to mediate regulation via positive feedback. Finally, in patients with GBM who did not respond to bevacizumab, a VEGF antagonist, EDN1 expression was higher than that in bevacizumab responders. Collectively, the present study demonstrated that EDN1 is a potent angiogenic factor inducing endothelial sprouting and may be a novel target for inhibiting glioma angiogenesis.

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