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Is Infantile Hemangioma a Neuroendocrine Tumor?

Infantile hemangioma (IH) is the most common infantile tumor, affecting 5–10% of newborns. Propranolol, a nonselective β-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 unders...

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Autores principales: Kaulanjan-Checkmodine, Priscilla, Oucherif, Sandra, Prey, Sorilla, Gontier, Etienne, Lacomme, Sabrina, Loot, Maya, Miljkovic-Licina, Marijana, Cario, Muriel, Léauté-Labrèze, Christine, Taieb, Alain, Moisan, François, Rezvani, Hamid Reza
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9104933/
https://www.ncbi.nlm.nih.gov/pubmed/35563552
http://dx.doi.org/10.3390/ijms23095140
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author Kaulanjan-Checkmodine, Priscilla
Oucherif, Sandra
Prey, Sorilla
Gontier, Etienne
Lacomme, Sabrina
Loot, Maya
Miljkovic-Licina, Marijana
Cario, Muriel
Léauté-Labrèze, Christine
Taieb, Alain
Moisan, François
Rezvani, Hamid Reza
author_facet Kaulanjan-Checkmodine, Priscilla
Oucherif, Sandra
Prey, Sorilla
Gontier, Etienne
Lacomme, Sabrina
Loot, Maya
Miljkovic-Licina, Marijana
Cario, Muriel
Léauté-Labrèze, Christine
Taieb, Alain
Moisan, François
Rezvani, Hamid Reza
author_sort Kaulanjan-Checkmodine, Priscilla
collection PubMed
description Infantile hemangioma (IH) is the most common infantile tumor, affecting 5–10% of newborns. Propranolol, a nonselective β-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’s sensitivity to propranolol depends on crosstalk between the endothelial cells, pericytes and telocytes in the context of a high local amount of local NA.
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spelling pubmed-91049332022-05-14 Is Infantile Hemangioma a Neuroendocrine Tumor? Kaulanjan-Checkmodine, Priscilla Oucherif, Sandra Prey, Sorilla Gontier, Etienne Lacomme, Sabrina Loot, Maya Miljkovic-Licina, Marijana Cario, Muriel Léauté-Labrèze, Christine Taieb, Alain Moisan, François Rezvani, Hamid Reza Int J Mol Sci Article Infantile hemangioma (IH) is the most common infantile tumor, affecting 5–10% of newborns. Propranolol, a nonselective β-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’s sensitivity to propranolol depends on crosstalk between the endothelial cells, pericytes and telocytes in the context of a high local amount of local NA. MDPI 2022-05-05 /pmc/articles/PMC9104933/ /pubmed/35563552 http://dx.doi.org/10.3390/ijms23095140 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kaulanjan-Checkmodine, Priscilla
Oucherif, Sandra
Prey, Sorilla
Gontier, Etienne
Lacomme, Sabrina
Loot, Maya
Miljkovic-Licina, Marijana
Cario, Muriel
Léauté-Labrèze, Christine
Taieb, Alain
Moisan, François
Rezvani, Hamid Reza
Is Infantile Hemangioma a Neuroendocrine Tumor?
title Is Infantile Hemangioma a Neuroendocrine Tumor?
title_full Is Infantile Hemangioma a Neuroendocrine Tumor?
title_fullStr Is Infantile Hemangioma a Neuroendocrine Tumor?
title_full_unstemmed Is Infantile Hemangioma a Neuroendocrine Tumor?
title_short Is Infantile Hemangioma a Neuroendocrine Tumor?
title_sort is infantile hemangioma a neuroendocrine tumor?
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9104933/
https://www.ncbi.nlm.nih.gov/pubmed/35563552
http://dx.doi.org/10.3390/ijms23095140
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