Biological and molecular characterization of a canine hemangiosarcoma-derived cell line

Douglas H. Thamm, Erin B. Dickerson, Nasim Akhtar, Rachel Lewis, Robert Auerbach, Stuart C. Helfand, E. Gregory MacEwen

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

Abstract

Canine hemangiosarcoma (HSA) is a devastating disease. Investigation of novel therapies has been limited by the limited availability of canine HSA-derived cell lines. We report the development of a canine HSA-derived cell line, DEN-HSA, which recapitulates features of angiogenic endothelium. DEN-HSA cells were derived from a spontaneous HSA arising in the kidney of a dog. DEN-HSA displayed surface molecules distinctive of endothelial histogenesis, including factor VIII-related antigen, ICAM-1 and αvβ3 integrin. In vitro, DEN-HSA formed microvascular tube-like structures on Matrigel®, and proliferated in response to a variety of angiogenic growth factors. The cells expressed mRNA and protein specific for bFGF and its receptors, and VEGF and its receptors, among others. DEN-HSA conditioned medium evoked a marked angiogenic response in a murine corneal pocket assay, indicating potent proangiogenic activity of substances secreted by this cell line. This research confirms the DEN-HSA cell line as endothelial in origin, suggests the presence of angiogenic growth factor autocrine loops, and offers the potential to utilize DEN-HSA cells for the study of novel therapies that modulate endothelial proliferation.

Original languageEnglish (US)
Pages (from-to)76-86
Number of pages11
JournalResearch in veterinary science
Volume81
Issue number1
DOIs
StatePublished - Aug 2006

Bibliographical note

Funding Information:
The authors dedicate this manuscript to their esteemed colleague and co-author, the late Dr. E. Gregory MacEwen, and to acknowledge the expert technical assistance of A.K. Marr, J.M. Schmidt, B. Charles and B. Shinners. This work was supported by the University of Wisconsin Animal Cancer Treatment Fund, and by a generous donation from Mr. A. Rolfe.

Keywords

  • Angiogenesis
  • Angiosarcoma
  • Dog
  • Endothelium

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