Propranolol, a nonselective β-adrenergic receptor blocker, is the first-line medical treatment for severe infantile hemangiomas (IH). We have shown in mice that propranolol-induced tumor growth inhibition was correlated with altered expression of Aquaporin-1 (AQP1), an aqueous channel modulated in angiogenesis and tumor cell migration. In IH, AQP1 made it possible to identify interstitial cell named telocytes (TC). TC are characterized by long cytoplasmic processes, the telopods, which form a three-dimensional communication network between cells, in organs such as skin, and in particular the dermal vessels. The localization and expression of AQP1 in TC is a marker of IH compared to the other hemangiomas. Defining new pool of cell types of interest in IH, we isolated, cultured and studied lesional: endothelial cells (EC), pericytes (PER) and TC. Using an in vitro angiogenesis model of IH that we have developed, we have studied the response to propranolol as a function of the expression of AQP1 modulated by shRNA. Then, since betablockers antagonize the effect of natural ADRB agonists, we postulated that catecholamines produced in situ in IH may have a role in propranolol response. Quantifying catecholamines in IH tissues, we found a high amount of noradrenaline (NA) in untreated proliferative IH compared to involuted IH or propranolol-treated IH. 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. We performed an in vitro angiogenesis assay in which IH-EC, PER and TC were incorporated. Results showed that the total number of tubes formed is sensitive to propranolol only when NA is added in the 3-cell model. We conclude that IH sensitivity to propranolol depends on crosstalk between lesional EC, PER and AQP1+ TC in the context of a high local amount of NA.

ESDR470 - Infantile hemangioma telocytes and noradrenaline are the prerequisite for response to propranolol

The scientific meeting of the European Society for Dermatological Research (ESDR) is held yearly, usually in September. With an international attendance of more than 1000 skin scientists from around the globe, the four-day event includes short oral presentations from peer-reviewed abstracts, keynote lectures from international experts, sponsored symposia, satellite programs, educational events as well as an important focus on posters, networking and building collaborations amongst scientists. For more information about this year’s meeting visit our website.