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Vet. Sci. 2015, 2(3), 270-292;

Beta Adrenergic Signaling: A Targetable Regulator of Angiosarcoma and Hemangiosarcoma

Department of Veterinary Clinical Sciences, University of Minnesota College of Veterinary Medicine, St. Paul, MN 55108, USA
Animal Cancer Care and Research Program, University of Minnesota, St. Paul, MN 55108, USA
Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA
Department of Biomedical Sciences, Texas Tech University Health Sciences Center, El Paso, TX 79912, USA
Author to whom correspondence should be addressed.
Academic Editor: Jaime F. Modiano
Received: 9 August 2015 / Revised: 5 September 2015 / Accepted: 8 September 2015 / Published: 21 September 2015
(This article belongs to the Special Issue Comparative Pathogenesis of Cancers in Animals and Humans)
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Human angiosarcomas and canine hemangiosarcomas are highly aggressive cancers thought to arise from cells of vascular origin. The pathological features, morphological organization, and clinical behavior of canine hemangiosarcomas are virtually indistinct from those of human angiosarcomas. Overall survival with current standard-of-care approaches remains dismal for both humans and dogs, and each is likely to succumb to their disease within a short duration. While angiosarcomas in humans are extremely rare, limiting their study and treatment options, canine hemangiosarcomas occur frequently. Therefore, studies of these sarcomas in dogs can be used to advance treatment approaches for both patient groups. Emerging data suggest that angiosarcomas and hemangiosarcomas utilize beta adrenergic signaling to drive their progression by regulating the tumor cell niche and fine-tuning cellular responses within the tumor microenvironment. These discoveries indicate that inhibition of beta adrenergic signaling could serve as an Achilles heel for these tumors and emphasize the need to design therapeutic strategies that target tumor cell and stromal cell constituents. In this review, we summarize recent discoveries and present new hypotheses regarding the roles of beta adrenergic signaling in angiosarcomas and hemangiosarcomas. Because the use of beta adrenergic receptor antagonists is well established in human and veterinary medicine, beta blockade could provide an immediate adjunct therapy for treatment along with a tangible opportunity to improve upon the outcomes of both humans and dogs with these diseases. View Full-Text
Keywords: angiosarcoma; beta adrenergic receptor; canine; CXCL12; CXCR4; hemangiosarcoma; S1P1; uPAR; vascular sarcoma angiosarcoma; beta adrenergic receptor; canine; CXCL12; CXCR4; hemangiosarcoma; S1P1; uPAR; vascular sarcoma

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Dickerson, E.B.; Bryan, B.A. Beta Adrenergic Signaling: A Targetable Regulator of Angiosarcoma and Hemangiosarcoma. Vet. Sci. 2015, 2, 270-292.

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