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

• Published in: Research in veterinary science 2006-08, Vol.81 (1), p.76-86
• Main Authors: Thamm, Douglas H., Dickerson, Erin B., Akhtar, Nasim, Lewis, Rachel, Auerbach, Robert, Helfand, Stuart C., MacEwen, E. Gregory
• Format: Article
• Language: English
• Subjects: Angiogenesis; angiogenesis growth factor; Angiogenic Proteins - analysis; Angiogenic Proteins - biosynthesis; Angiosarcoma; Animals; antigens; Cancer; Cancer therapies; Cell adhesion & migration; Cell culture; cell lines; Cell Proliferation; cell surface molecules; disease models; Dog; Dogs; Endothelium; Flow Cytometry; growth factors; hemangiosarcoma; Hemangiosarcoma - pathology; Hemangiosarcoma - veterinary; histopathology; Immunohistochemistry; in vitro studies; Insulin-like growth factors; integrins; Kidney Neoplasms - pathology; Kidney Neoplasms - veterinary; messenger RNA; Neovascularization, Pathologic; outer membrane proteins; pets; protein synthesis; RNA, Messenger - biosynthesis; Rodents; Tumor Cells, Cultured - metabolism; Tumors; vascular endothelial growth factors; Veterinary medicine
• ISSN: 0034-5288; 1532-2661
• DOI: 10.1016/j.rvsc.2005.09.005

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 α vβ 3 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.