Beta adrenergic signaling: A targetable regulator of angiosarcoma and hemangiosarcoma

Erin B. Dickerson, Brad A. Bryan

Research output: Contribution to journalReview articlepeer-review

4 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)270-292
Number of pages23
JournalVeterinary Sciences
Volume2
Issue number3
DOIs
StatePublished - Sep 1 2015

Bibliographical note

Funding Information:
This work was partially supported by the Office of the Vice President for Research, University of Minnesota, award #21873, Morris Animal Foundation D13CA-062 and D14CA-047, AKC Canine Health Foundation, Grant 01759, the Rein in Sarcoma Foundation, P30 CA077598 (NCI Core Support Grant for the Masonic Cancer Center), National Heart, Lung, and Blood Institute grant HL098931, a grant from the Sarcoma Foundation of America, and a Liddy Shriver Sarcoma Initiative grant. Thank you to Jong Hyuk Kim, Derek Korpela, Ashley J. Graef, and Jaime F. Modiano for the critical reading of this manuscript, and to David Mottet for his assistance with the artistic design of the figures.

Publisher Copyright:
© 2015 by the authors.

Keywords

  • Angiosarcoma
  • Beta adrenergic receptor
  • CXCL12
  • CXCR4
  • Canine
  • Hemangiosarcoma
  • S1P1
  • UPAR
  • Vascular sarcoma

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