Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 23, Issue 9, Pages -Publisher
MDPI
DOI: 10.3390/ijms23095140
Keywords
hemangioma; propranolol; betablocker; catecholamines; adrenergic; telocytes
Funding
- ANR
- Ligue Nationale contre le Cancer, L'Oreal La Roche Posay, Laboratoires Pierre Fabre
- Fondation Association pour la Recherche contre le Cancer
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The study reveals that the catecholamine noradrenaline plays a role in the response of infantile hemangioma (IH) to propranolol treatment. IH tissues contain a higher amount of noradrenaline compared to involuted IHs or propranolol-treated IHs. The sensitivity of IH to propranolol depends on the crosstalk between endothelial cells, pericytes, and telocytes in the presence of a high local amount of noradrenaline.
Infantile hemangioma (IH) is the most common infantile tumor, affecting 5-10% of newborns. Propranolol, a nonselective beta-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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