Targeting of Beta Adrenergic Receptors Results in Therapeutic Efficacy against Models of Hemangioendothelioma and Angiosarcoma

Jessica M. Stiles, Clarissa Amaya, Steven Rains, Dolores Diaz, Robert Pham, James Battiste, Jaime F. Modiano, Victor Kokta, Laura E. Boucheron, Dianne C. Mitchell, Brad A. Bryan

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

Therapeutic targeting of the beta-adrenergic receptors has recently shown remarkable efficacy in the treatment of benign vascular tumors such as infantile hemangiomas. As infantile hemangiomas are reported to express high levels of beta adrenergic receptors, we examined the expression of these receptors on more aggressive vascular tumors such as hemangioendotheliomas and angiosarcomas, revealing beta 1, 2, and 3 receptors were indeed present and therefore aggressive vascular tumors may similarly show increased susceptibility to the inhibitory effects of beta blockade. Using a panel of hemangioendothelioma and angiosarcoma cell lines, we demonstrate that beta adrenergic inhibition blocks cell proliferation and induces apoptosis in a dose dependent manner. Beta blockade is selective for vascular tumor cells over normal endothelial cells and synergistically effective when combined with standard chemotherapeutic or cytotoxic agents. We demonstrate that inhibition of beta adrenergic signaling induces large scale changes in the global gene expression patterns of vascular tumors, including alterations in the expression of established cell cycle and apoptotic regulators. Using in vivo tumor models we demonstrate that beta blockade shows remarkable efficacy as a single agent in reducing the growth of angiosarcoma tumors. In summary, these experiments demonstrate the selective cytotoxicity and tumor suppressive ability of beta adrenergic inhibition on malignant vascular tumors and have laid the groundwork for a promising treatment of angiosarcomas in humans.

Original languageEnglish (US)
Article numbere60021
JournalPLoS One
Volume8
Issue number3
DOIs
StatePublished - Mar 28 2013

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Hemangioendothelioma
Hemangiosarcoma
Receptors, Adrenergic, beta
Tumors
blood vessels
therapeutics
neoplasms
Blood Vessels
Neoplasms
hemangioma
Adrenergic Agents
Therapeutics
Cells
Hemangioma
receptors
reducing agents
beta adrenergic receptors
global change
Reducing Agents
Endothelial cells

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Targeting of Beta Adrenergic Receptors Results in Therapeutic Efficacy against Models of Hemangioendothelioma and Angiosarcoma. / Stiles, Jessica M.; Amaya, Clarissa; Rains, Steven; Diaz, Dolores; Pham, Robert; Battiste, James; Modiano, Jaime F.; Kokta, Victor; Boucheron, Laura E.; Mitchell, Dianne C.; Bryan, Brad A.

In: PLoS One, Vol. 8, No. 3, e60021, 28.03.2013.

Research output: Contribution to journalArticle

Stiles, JM, Amaya, C, Rains, S, Diaz, D, Pham, R, Battiste, J, Modiano, JF, Kokta, V, Boucheron, LE, Mitchell, DC & Bryan, BA 2013, 'Targeting of Beta Adrenergic Receptors Results in Therapeutic Efficacy against Models of Hemangioendothelioma and Angiosarcoma', PLoS One, vol. 8, no. 3, e60021. https://doi.org/10.1371/journal.pone.0060021
Stiles, Jessica M. ; Amaya, Clarissa ; Rains, Steven ; Diaz, Dolores ; Pham, Robert ; Battiste, James ; Modiano, Jaime F. ; Kokta, Victor ; Boucheron, Laura E. ; Mitchell, Dianne C. ; Bryan, Brad A. / Targeting of Beta Adrenergic Receptors Results in Therapeutic Efficacy against Models of Hemangioendothelioma and Angiosarcoma. In: PLoS One. 2013 ; Vol. 8, No. 3.
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