{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T07:37:15Z","timestamp":1781163435436,"version":"3.54.1"},"reference-count":42,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2022,5,5]],"date-time":"2022-05-05T00:00:00Z","timestamp":1651708800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001665","name":"ANR \u201cBETASKIN2\u201d","doi-asserted-by":"publisher","award":["ANR-12-BSV1-0021-01"],"award-info":[{"award-number":["ANR-12-BSV1-0021-01"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Infantile hemangioma (IH) is the most common infantile tumor, affecting 5\u201310% of newborns. Propranolol, a nonselective \u03b2-adrenergic receptor (ADRB) antagonist, is currently the first-line treatment for severe IH; however, both its mechanism of action and its main cellular target remain poorly understood. Since betablockers can antagonize the effect of natural ADRB agonists, we postulated that the catecholamine produced in situ in IH may have a role in the propranolol response. By quantifying catecholamines in the IH tissues, we found a higher amount of noradrenaline (NA) in untreated proliferative IHs than in involuted IHs or propranolol-treated IHs. We further found that the first three enzymes of the catecholamine biosynthesis pathway are expressed by IH cells and that their levels are reduced in propranolol-treated tumors. To study the role of NA in the pathophysiology of IH and its response to propranolol, we performed an in vitro angiogenesis assay in which IH-derived endothelial cells, pericytes and\/or telocytes were incorporated. The results showed that the total tube formation is sensitive to propranolol only when exogenous NA is added in the three-cell model. We conclude that the IH\u2019s sensitivity to propranolol depends on crosstalk between the endothelial cells, pericytes and telocytes in the context of a high local amount of local NA.<\/jats:p>","DOI":"10.3390\/ijms23095140","type":"journal-article","created":{"date-parts":[[2022,5,5]],"date-time":"2022-05-05T13:10:26Z","timestamp":1651756226000},"page":"5140","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Is Infantile Hemangioma a Neuroendocrine Tumor?"],"prefix":"10.3390","volume":"23","author":[{"given":"Priscilla","family":"Kaulanjan-Checkmodine","sequence":"first","affiliation":[{"name":"BRIC, UMR 1312, Inserm, University Bordeaux, F-33076 Bordeaux, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6462-4363","authenticated-orcid":false,"given":"Sandra","family":"Oucherif","sequence":"additional","affiliation":[{"name":"BRIC, UMR 1312, Inserm, University Bordeaux, F-33076 Bordeaux, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sorilla","family":"Prey","sequence":"additional","affiliation":[{"name":"BRIC, UMR 1312, Inserm, University Bordeaux, F-33076 Bordeaux, France"},{"name":"Service de Dermatologie Adulte et P\u00e9diatrique, CHU de Bordeaux, F-33000 Bordeaux, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Etienne","family":"Gontier","sequence":"additional","affiliation":[{"name":"Electron Microscopy Unit, Bordeaux Imaging Center, F-33076 Bordeaux, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0752-1362","authenticated-orcid":false,"given":"Sabrina","family":"Lacomme","sequence":"additional","affiliation":[{"name":"Electron Microscopy Unit, Bordeaux Imaging Center, F-33076 Bordeaux, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maya","family":"Loot","sequence":"additional","affiliation":[{"name":"CHU de Bordeaux, Service de Chirurgie P\u00e9diatrique, F-33000 Bordeaux, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9023-2208","authenticated-orcid":false,"given":"Marijana","family":"Miljkovic-Licina","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology, University of Geneva Medical School, Rue Michel-Servet 1, CH-1211 Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muriel","family":"Cario","sequence":"additional","affiliation":[{"name":"BRIC, UMR 1312, Inserm, University Bordeaux, F-33076 Bordeaux, France"},{"name":"Centre de R\u00e9f\u00e9rence pour les Maladies Rares de la Peau, CHU de Bordeaux, INSERM U1312, F-33000 Bordeaux, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"L\u00e9aut\u00e9-Labr\u00e8ze","sequence":"additional","affiliation":[{"name":"BRIC, UMR 1312, Inserm, University Bordeaux, F-33076 Bordeaux, France"},{"name":"Service de Dermatologie Adulte et P\u00e9diatrique, CHU de Bordeaux, F-33000 Bordeaux, France"},{"name":"Centre de R\u00e9f\u00e9rence pour les Maladies Rares de la Peau, CHU de Bordeaux, INSERM U1312, F-33000 Bordeaux, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0928-8608","authenticated-orcid":false,"given":"Alain","family":"Taieb","sequence":"additional","affiliation":[{"name":"BRIC, UMR 1312, Inserm, University Bordeaux, F-33076 Bordeaux, France"},{"name":"Service de Dermatologie Adulte et P\u00e9diatrique, CHU de Bordeaux, F-33000 Bordeaux, France"},{"name":"Centre de R\u00e9f\u00e9rence pour les Maladies Rares de la Peau, CHU de Bordeaux, INSERM U1312, F-33000 Bordeaux, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2680-7497","authenticated-orcid":false,"given":"Fran\u00e7ois","family":"Moisan","sequence":"additional","affiliation":[{"name":"BRIC, UMR 1312, Inserm, University Bordeaux, F-33076 Bordeaux, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hamid Reza","family":"Rezvani","sequence":"additional","affiliation":[{"name":"BRIC, UMR 1312, Inserm, University Bordeaux, F-33076 Bordeaux, France"},{"name":"Centre de R\u00e9f\u00e9rence pour les Maladies Rares de la Peau, CHU de Bordeaux, INSERM U1312, F-33000 Bordeaux, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1053\/j.sempedsurg.2014.06.016","article-title":"ISSVA classification","volume":"23","author":"Dasgupta","year":"2014","journal-title":"Semin. 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