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

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 recep...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3610939/
https://www.ncbi.nlm.nih.gov/pubmed/23555867
http://dx.doi.org/10.1371/journal.pone.0060021
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author 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.
author_facet 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.
author_sort Stiles, Jessica M.
collection PubMed
description 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.
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spelling pubmed-36109392013-04-03 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. PLoS One Research Article 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. Public Library of Science 2013-03-28 /pmc/articles/PMC3610939/ /pubmed/23555867 http://dx.doi.org/10.1371/journal.pone.0060021 Text en © 2013 Stiles et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
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
title Targeting of Beta Adrenergic Receptors Results in Therapeutic Efficacy against Models of Hemangioendothelioma and Angiosarcoma
title_full Targeting of Beta Adrenergic Receptors Results in Therapeutic Efficacy against Models of Hemangioendothelioma and Angiosarcoma
title_fullStr Targeting of Beta Adrenergic Receptors Results in Therapeutic Efficacy against Models of Hemangioendothelioma and Angiosarcoma
title_full_unstemmed Targeting of Beta Adrenergic Receptors Results in Therapeutic Efficacy against Models of Hemangioendothelioma and Angiosarcoma
title_short Targeting of Beta Adrenergic Receptors Results in Therapeutic Efficacy against Models of Hemangioendothelioma and Angiosarcoma
title_sort targeting of beta adrenergic receptors results in therapeutic efficacy against models of hemangioendothelioma and angiosarcoma
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3610939/
https://www.ncbi.nlm.nih.gov/pubmed/23555867
http://dx.doi.org/10.1371/journal.pone.0060021
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