ArticleProceedings of the National Academy of Sciences of the United States of America2021
Critical role of Aquaporin-1 and telocytes in infantile hemangioma response to propranolol beta blockade.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 38 citations in OpenAlex.
- Review
- Targeted Therapies in Infantile Hemangiomas and Vascular Malformations: From β-Blockers to PI3K/AKT/mTOR Inhibitors.Journal of cellular and molecular medicine · 2026Review
- Key cellular subpopulations and mechanisms of propranolol in infantile hemangioma: insights from single-cell omics.Frontiers in medicine · 2026Review
- Immune microenvironment of infantile hemangioma: cellular dynamics, molecular networks, and emerging immunomodulatory strategies.Frontiers in immunology · 2026Review
- Cell type-specific pharmacological modulation of the neuro-immune axis: the role of ADRB2 signaling in reshaping the tumor ecosystem.Frontiers in pharmacology · 2026Review
- Decoding infantile hemangioma: cellular dynamics, molecular signals, and microenvironmental influences.Frontiers in oncology · 2025Review
- Topical propranolol for infantile hemangioma: a comprehensive review of mechanisms, clinical efficacy, and novel formulations.Frontiers in pediatrics · 2025Review
- Developmental characteristics of cutaneous telocytes in late embryos of the silky fowl.European journal of histochemistry : EJH · 2024Article
- Infantile hemangiomas: a dermatologist's perspective.European journal of pediatrics · 2024Review
- Infantile hemangioma: the common and enigmatic vascular tumor.The Journal of clinical investigation · 2024Review
- Heart failure pharmacotherapy and cancer: pathways and pre-clinical/clinical evidence.European heart journal · 2024Review
- Clinical characteristics of infantile haemangioma in twins: a retrospective study.BMC pediatrics · 2024Article
- Aquaporin 1 overexpression may enhance glioma tumorigenesis by interacting with the transcriptional regulation networks of Foxo4, Maz, and E2F families.Chinese neurosurgical journal · 2023Article
- Global research trends of infantile hemangioma: A bibliometric and visualization analysis from 2000 to 2022.Heliyon · 2023Article
- Infantile hemangioma models: is the needle in a haystack?Journal of translational medicine · 2023Review
- CD146Frontiers in oncology · 2023Article
- Editorial: Advances in the medical management of infantile hemangioma.Frontiers in oncology · 2023Article
- Review
- Three-Dimensional Microtumor Formation of Infantile Hemangioma-Derived Endothelial Cells for Mechanistic Exploration and Drug Screening.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Medical management of vascular anomalies of the head and neck.Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology · 2022Review
Corrections and comments
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Authors and funding
18 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.