title: Propranolol responsiveness in vascular tumors is not determined by qualitative differences in adrenergic receptors.
abstract: Propranolol, a beta 1 (ADBR1) and beta 2 (ADBR2) adrenergic receptor blocker, accelerates regression of proliferating infantile hemangiomas (IH-P) while not affecting non-involuting congenital hemangiomas (NICH) and nonproliferating IH (IH-NP). To determine the expression of ADBRs in vascular tumors, immunofluorescent staining and confocal microscopy were employed to determine the in situ cellular distribution of ADBRs in formalin-fixed paraffin-embedded tissue sections of IH-P, IH-NP, and NICH. In situ cellular proliferation, indexed by Ki-67 expression, distinguished IH-P (n = 3) from both IH-NP (n = 3) and NICH (n = 2). In IH-P, IH-NP, and NICH tumor sections, both ADBR1 and ADBR2 were co-localized in both endothelial cells (ECs; GLUT1(+) in IH; CD31+ in NICH) and pericytes (smooth muscle actin). We tentatively conclude that either EC and/or pericytes in IH-P could be target(s) of propranolol. Cell proliferation, but not absence of either class of ADBR, distinguished the propranolol responsive IH-P from the nonresponsive IH-NP and NICH.
authors.affiliation: Vascular Anomalies Program, Seattle Children's Hospital, Seattle, Washingon, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Boucek
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Kirsh
authors.forename: Mark W
authors.initials: MW
authors.lastname: Majesky
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Perkins
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D018613:Microscopy, Confocal; D011433:Propranolol / Q000008:administration & dosage*; D011941:Receptors, Adrenergic / Q000096:biosynthesis* / Q000187:drug effects; D019043:Vascular Neoplasms / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000319:Adrenergic beta-Antagonists; D011941:Receptors, Adrenergic; D011433:Propranolol
keywords: adrenergic; cell; congenital hemangioma; immunostaining; infantile hemangioma; mechanism; propranolol