气候变化领域集成服务门户(CCPortal): Critical role of Aquaporin-1 and telocytes in infantile hemangioma response to propranolol beta blockade

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DOI	10.1073/pnas.2018690118
	Critical role of Aquaporin-1 and telocytes in infantile hemangioma response to propranolol beta blockade
	Moisan F.; Oucherif S.; Kaulanjan-Checkmodine P.; Prey S.; Rousseau B.; Bonneu M.; Claverol S.; Gontier E.; Lacomme S.; Dousset L.; Couffinhal T.; Toutain J.; Loot M.; Cario-André M.; Jullié M.-L.; Léauté-Labrèze C.; Taieb A.; Rezvani H.R.
发表日期	2021
ISSN	00278424
卷号	118 期号:7
英文摘要	Propranolol, a nonselective β-adrenergic receptor (ADRB) antagonist, is the first-line therapy for severe infantile hemangiomas (IH). Since the incidental discovery of propranolol efficacy in IH, preclinical and clinical investigations have shown evidence of adjuvant propranolol response in some malignant tumors. However, the mechanism for propranolol antitumor effect is still largely unknown, owing to the absence of a tumor model responsive to propranolol at nontoxic concentrations. Immunodeficient mice engrafted with different human tumor cell lines were treated with anti-VEGF bevacizumab to create a model sensitive to propranolol. Proteomics analysis was used to reveal propranolol-mediated protein alteration correlating with tumor growth inhibition, and Aquaporin-1 (AQP1), a water channel modulated in tumor cell migration and invasion, was identified. IH tissues and cells were then functionally investigated. Our functional protein association networks analysis and knockdown of ADRB2 and AQP1 indicated that propranolol treatment and AQP1 down-regulation trigger the same pathway, suggesting that AQP1 is a major driver of beta-blocker antitumor response. Examining AQP1 in human hemangioma samples, we found it exclusively in a perivascular layer, so far unrecognized in IH, made of telocytes (TCs). Functional in vitro studies showed that AQP1-positive TCs play a critical role in IH response to propranolol and that modulation of AQP1 in IH-TC by propranolol or shAQP1 decreases capillary-like tube formation in a Matrigel-based angiogenesis assay. We conclude that IH sensitivity to propranolol may rely, at least in part, on a cross talk between lesional vascular cells and stromal TCs. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Hemangioma \| propranolol \| telocyte \| aquaporin-1 \| angiogenesis
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180604
作者单位	Inserm, Biothérapie des Maladies Génétiques Inflammatoires et Cancers (BMGIC), UMR 1035, University of Bordeaux, Bordeaux, F-33076, France; Service de Dermatologie Adulte et Pédiatrique, Centre Hospitalier Universitaire (CHU) de Bordeaux, Bordeaux, F-33000, France; Animalerie A2, University of Bordeaux, Bordeaux, F-33000, France; Plateforme de protéomique, Centre de Génomique Fonctionnelle de Bordeaux, University of Bordeaux, Bordeaux, F-33076, France; Bordeaux Imaging Center (BIC)–Electron Microscopy Unit, University of Bordeaux, Bordeaux, F-33076, France; Inserm U 1034, University of Bordeaux, Pessac, F-33600, France; Service de Génétique Médicale, CHU de Bordeaux, Bordeaux, F-33000, France; Service de Chirurgie Pédiatrique, CHU de Bordeaux, Bordeaux, F-33000, France; Centre de Référence pour les Maladies Rares de la Peau, CHU Bordeaux, Bordeaux, F-33000, France; Service d’anatomopathologie, CHU de Bordeaux, Bordeaux, F-33000, France
推荐引用方式 GB/T 7714	Moisan F.,Oucherif S.,Kaulanjan-Checkmodine P.,et al. Critical role of Aquaporin-1 and telocytes in infantile hemangioma response to propranolol beta blockade[J],2021,118(7).
APA	Moisan F..,Oucherif S..,Kaulanjan-Checkmodine P..,Prey S..,Rousseau B..,...&Rezvani H.R..(2021).Critical role of Aquaporin-1 and telocytes in infantile hemangioma response to propranolol beta blockade.Proceedings of the National Academy of Sciences of the United States of America,118(7).
MLA	Moisan F.,et al."Critical role of Aquaporin-1 and telocytes in infantile hemangioma response to propranolol beta blockade".Proceedings of the National Academy of Sciences of the United States of America 118.7(2021).