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.