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- Title
Is Infantile Hemangioma a Neuroendocrine Tumor?
- Authors
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
- Abstract
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.
- Subjects
NEUROENDOCRINE tumors; HEMANGIOMAS; ENDOTHELIAL cells; PROPRANOLOL; PERICYTES; NORADRENALINE; BETA adrenoceptors
- Publication
International Journal of Molecular Sciences, 2022, Vol 23, Issue 9, p5140
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms23095140