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

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 angiogenesis and cell migration. In IH, AQP1 made it possible to identify interstitial named telocytes (TC). TC are characterized by long cytoplasmic processes, telopods, which form three-dimensional communication network between cells, organs such as skin, particular dermal vessels. The localization marker IH compared other hemangiomas. Defining new pool types interest we isolated, cultured studied lesional: endothelial cells (EC), pericytes (PER) TC. Using vitro model developed, response propranolol function shRNA. Then, since betablockers antagonize effect natural ADRB agonists, postulated catecholamines produced situ may role response. Quantifying tissues, found high amount noradrenaline (NA) untreated proliferative involuted or propranolol-treated IH. further first three enzymes catecholamine biosynthesis pathway expressed their levels reduced tumors. performed assay IH-EC, PER were incorporated. Results showed total number tubes formed sensitive only when NA added 3-cell model. conclude sensitivity depends on crosstalk lesional EC, AQP1+ context local NA.