Propranolol treatment of infantile hemangioma endothelial cells: A molecular analysis

  • Authors:
    • Jessica Stiles
    • Clarissa Amaya
    • Robert Pham
    • Rebecca K. Rowntree
    • Mary Lacaze
    • Arlynn Mulne
    • Joyce Bischoff
    • Victor Kokta
    • Laura E. Boucheron
    • Dianne C. Mitchell
    • Brad A. Bryan
  • View Affiliations

  • Published online on: August 3, 2012     https://doi.org/10.3892/etm.2012.654
  • Pages: 594-604
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Abstract

Infantile hemangiomas (IHs) are non-malignant, largely cutaneous vascular tumors affecting approximately 5-10% of children to varying degrees. During the first year of life, these tumors are strongly proliferative, reaching an average size ranging from 2 to 20 cm. These lesions subsequently stabilize, undergo a spontaneous slow involution and are fully regressed by 5 to 10 years of age. Systemic treatment of infants with the non-selective β-adrenergic receptor blocker, propranolol, has demonstrated remarkable efficacy in reducing the size and appearance of IHs. However, the mechanism by which this occurs is largely unknown. In this study, we sought to understand the molecular mechanisms underlying the effectiveness of β blocker treatment in IHs. Our data reveal that propranolol treatment of IH endothelial cells, as well as a panel of normal primary endothelial cells, blocks endothelial cell proliferation, migration, and formation of the actin cytoskeleton coincident with alterations in vascular endothelial growth factor receptor-2 (VEGFR-2), p38 and cofilin signaling. Moreover, propranolol induces major alterations in the protein levels of key cyclins and cyclin-dependent kinase inhibitors, and modulates global gene expression patterns with a particular affect on genes involved in lipid/sterol metabolism, cell cycle regulation, angiogenesis and ubiquitination. Interestingly, the effects of propranolol were endothelial cell-type independent, affecting the properties of IH endothelial cells at similar levels to that observed in neonatal dermal microvascular and coronary artery endothelial cells. This data suggests that while propranolol markedly inhibits hemangioma and normal endothelial cell function, its lack of endothelial cell specificity hints that the efficacy of this drug in the treatment of IHs may be more complex than simply blockage of endothelial function as previously believed.
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October 2012
Volume 4 Issue 4

Print ISSN: 1792-0981
Online ISSN:1792-1015

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Spandidos Publications style
Stiles J, Amaya C, Pham R, Rowntree RK, Lacaze M, Mulne A, Bischoff J, Kokta V, Boucheron LE, Mitchell DC, Mitchell DC, et al: Propranolol treatment of infantile hemangioma endothelial cells: A molecular analysis. Exp Ther Med 4: 594-604, 2012.
APA
Stiles, J., Amaya, C., Pham, R., Rowntree, R.K., Lacaze, M., Mulne, A. ... Bryan, B. . (2012). Propranolol treatment of infantile hemangioma endothelial cells: A molecular analysis. Experimental and Therapeutic Medicine, 4, 594-604. https://doi.org/10.3892/etm.2012.654
MLA
Stiles, J., Amaya, C., Pham, R., Rowntree, R. K., Lacaze, M., Mulne, A., Bischoff, J., Kokta, V., Boucheron, L. E., Mitchell, D. C., Bryan, B. ."Propranolol treatment of infantile hemangioma endothelial cells: A molecular analysis". Experimental and Therapeutic Medicine 4.4 (2012): 594-604.
Chicago
Stiles, J., Amaya, C., Pham, R., Rowntree, R. K., Lacaze, M., Mulne, A., Bischoff, J., Kokta, V., Boucheron, L. E., Mitchell, D. C., Bryan, B. ."Propranolol treatment of infantile hemangioma endothelial cells: A molecular analysis". Experimental and Therapeutic Medicine 4, no. 4 (2012): 594-604. https://doi.org/10.3892/etm.2012.654