Biological and molecular characterization of a canine hemangiosarcoma-derived cell line.
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 alpha(v)beta3 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.
Thamm
Douglas H
DH
Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, 53706, USA. dthamm@colostate.edu
Dickerson
Erin B
EB
Akhtar
Nasim
N
Lewis
Rachel
R
Auerbach
Robert
R
Helfand
Stuart C
SC
MacEwen
E Gregory
EG
D042501:Angiogenic Proteins / Q000032:analysis / Q000096:biosynthesis; D000818:Animals; D049109:Cell Proliferation; D004285:Dogs; D005434:Flow Cytometry; D006394:Hemangiosarcoma / Q000473:pathology* / Q000662:veterinary*; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000473:pathology* / Q000662:veterinary*; D009389:Neovascularization, Pathologic; D012333:RNA, Messenger / Q000096:biosynthesis; D014407:Tumor Cells, Cultured / Q000378:metabolism*
D042501:Angiogenic Proteins; D012333:RNA, Messenger