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Propranolol inhibits stemness of hemangioma through Jagged1

BACKGROUND: Propranolol is used clinically to treat infantile hemangioma (IH), although the exact mechanism that underlies its effectiveness is not fully understood. The Jagged1/Notch signaling pathway is downstream of the β2-adrenergic receptor (β2-AR). Propranolol is a non-selective β2-AR blocker...

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Autores principales: Ma, Xiaorong, Lv, Kaiyang, Wu, Liming, Ouyang, Tianxiang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: AME Publishing Company 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8667105/
https://www.ncbi.nlm.nih.gov/pubmed/34988191
http://dx.doi.org/10.21037/atm-21-5563
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author Ma, Xiaorong
Lv, Kaiyang
Wu, Liming
Ouyang, Tianxiang
author_facet Ma, Xiaorong
Lv, Kaiyang
Wu, Liming
Ouyang, Tianxiang
author_sort Ma, Xiaorong
collection PubMed
description BACKGROUND: Propranolol is used clinically to treat infantile hemangioma (IH), although the exact mechanism that underlies its effectiveness is not fully understood. The Jagged1/Notch signaling pathway is downstream of the β2-adrenergic receptor (β2-AR). Propranolol is a non-selective β2-AR blocker that was shown to inhibit demethylation adrenaline-induced Jagged1 expression. A previous study has shown that propranolol dose-dependently inhibits the growth of IH. However, the effects of propranolol on stemness of IH are not known and are thus addressed in the current study. METHODS: We analyzed the expression of Jagged1 and Notch3 in IH specimens, using genetic tools to alter Notch signaling. The transduced IH cells were treated with different doses of propranolol, and the effects on IH cell proliferation, migration, and potential for tumor sphere formation were investigated. The effects of altered Notch signaling on tumor formation in vivo were also assessed. RESULTS: Notch3 and Jagged1 were significantly upregulated in IH. Augmented Notch signaling in IH cells increased cell proliferation, migration, the potential for tumor sphere formation and in vivo tumor formation. On the other hand, reduced Notch signaling in IH cells decreased cell proliferation, migration, the potential for tumor sphere formation and in vivo tumor formation. CONCLUSIONS: Jagged1/Notch signaling regulated the stemness of IH, and propranolol inhibited it through suppression of Notch signaling.
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spelling pubmed-86671052022-01-04 Propranolol inhibits stemness of hemangioma through Jagged1 Ma, Xiaorong Lv, Kaiyang Wu, Liming Ouyang, Tianxiang Ann Transl Med Original Article BACKGROUND: Propranolol is used clinically to treat infantile hemangioma (IH), although the exact mechanism that underlies its effectiveness is not fully understood. The Jagged1/Notch signaling pathway is downstream of the β2-adrenergic receptor (β2-AR). Propranolol is a non-selective β2-AR blocker that was shown to inhibit demethylation adrenaline-induced Jagged1 expression. A previous study has shown that propranolol dose-dependently inhibits the growth of IH. However, the effects of propranolol on stemness of IH are not known and are thus addressed in the current study. METHODS: We analyzed the expression of Jagged1 and Notch3 in IH specimens, using genetic tools to alter Notch signaling. The transduced IH cells were treated with different doses of propranolol, and the effects on IH cell proliferation, migration, and potential for tumor sphere formation were investigated. The effects of altered Notch signaling on tumor formation in vivo were also assessed. RESULTS: Notch3 and Jagged1 were significantly upregulated in IH. Augmented Notch signaling in IH cells increased cell proliferation, migration, the potential for tumor sphere formation and in vivo tumor formation. On the other hand, reduced Notch signaling in IH cells decreased cell proliferation, migration, the potential for tumor sphere formation and in vivo tumor formation. CONCLUSIONS: Jagged1/Notch signaling regulated the stemness of IH, and propranolol inhibited it through suppression of Notch signaling. AME Publishing Company 2021-11 /pmc/articles/PMC8667105/ /pubmed/34988191 http://dx.doi.org/10.21037/atm-21-5563 Text en 2021 Annals of Translational Medicine. All rights reserved. https://creativecommons.org/licenses/by-nc-nd/4.0/Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Original Article
Ma, Xiaorong
Lv, Kaiyang
Wu, Liming
Ouyang, Tianxiang
Propranolol inhibits stemness of hemangioma through Jagged1
title Propranolol inhibits stemness of hemangioma through Jagged1
title_full Propranolol inhibits stemness of hemangioma through Jagged1
title_fullStr Propranolol inhibits stemness of hemangioma through Jagged1
title_full_unstemmed Propranolol inhibits stemness of hemangioma through Jagged1
title_short Propranolol inhibits stemness of hemangioma through Jagged1
title_sort propranolol inhibits stemness of hemangioma through jagged1
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8667105/
https://www.ncbi.nlm.nih.gov/pubmed/34988191
http://dx.doi.org/10.21037/atm-21-5563
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