β1-Adrenoceptor mRNA level reveals distinctions between infantile hemangioma and vascular malformations

Pediatr Res. 2013 Apr;73(4 Pt 1):409-13. doi: 10.1038/pr.2013.16. Epub 2013 Jan 31.

Abstract

Background: Infantile hemangioma (IH) is the most frequent vascular tumor of early childhood. Recently, propranolol, a nonselective β1- and β2-adrenoceptor inhibitor, was introduced into the therapy of severe proliferating IH with excellent results. However, the underlying mechanism of action of propranolol is still unclear.

Methods: We performed immunohistochemistry for cluster of differentiation 31 (CD31), D2-40, glucose transporter-1 (GLUT-1), and Ki67 in order to characterize 21 vascular anomalies (nine IH, seven venous malformations (VMs), and five lymphatic malformations (LMs)). Furthermore, we analyzed the expression of β1-, β2-, and β3-adrenoceptor mRNA in these specimens as well as in hemangioma-derived stem cells by quantitative real-time PCR (qPCR).

Results: We show that the expression of β1-adrenoceptor mRNA is 10.7-fold higher in IH independent of the proliferative or regressive phase as well as 2.5-fold higher in hemangioma-derived stem cells as compared with β2-adrenoceptor mRNA. In LM, the expression of β2-adrenoceptor mRNA was ninefold higher than that of β1-adrenoceptor mRNA. VM showed low expression levels of all β-adrenoceptor mRNAs, and β3-adrenoceptor mRNA was hardly detectable in any specimens examined.

Conclusion: These results provide the first evidence of distinctions between IH and vascular malformations with regard to β-adrenoceptor subtype mRNA levels.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Antibodies, Monoclonal, Murine-Derived
  • Cells, Cultured
  • Child
  • Child, Preschool
  • Genetic Markers
  • Glucose Transporter Type 1 / metabolism
  • Hemangioma, Capillary / genetics*
  • Hemangioma, Capillary / metabolism
  • Hemangioma, Capillary / pathology
  • Humans
  • Immunohistochemistry
  • Infant
  • Infant, Newborn
  • Ki-67 Antigen / metabolism
  • Neoplastic Stem Cells / metabolism*
  • Neoplastic Stem Cells / pathology
  • Neoplastic Syndromes, Hereditary / genetics*
  • Neoplastic Syndromes, Hereditary / metabolism
  • Neoplastic Syndromes, Hereditary / pathology
  • Platelet Endothelial Cell Adhesion Molecule-1 / metabolism
  • RNA, Messenger / metabolism*
  • Real-Time Polymerase Chain Reaction
  • Receptors, Adrenergic, beta-1 / genetics*
  • Receptors, Adrenergic, beta-2 / genetics
  • Receptors, Adrenergic, beta-3 / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Vascular Malformations / genetics*
  • Vascular Malformations / metabolism
  • Vascular Malformations / pathology

Substances

  • ADRB1 protein, human
  • ADRB2 protein, human
  • ADRB3 protein, human
  • Antibodies, Monoclonal, Murine-Derived
  • Genetic Markers
  • Glucose Transporter Type 1
  • Ki-67 Antigen
  • Platelet Endothelial Cell Adhesion Molecule-1
  • RNA, Messenger
  • Receptors, Adrenergic, beta-1
  • Receptors, Adrenergic, beta-2
  • Receptors, Adrenergic, beta-3
  • SLC2A1 protein, human
  • monoclonal antibody D2-40

Supplementary concepts

  • Hemangioma, capillary infantile