Canine malignant hemangiosarcoma as a model of primitive angiogenic endothelium.

TitleCanine malignant hemangiosarcoma as a model of primitive angiogenic endothelium.
Publication TypeJournal Article
Year of Publication2004
AuthorsFosmire SP, Dickerson EB, Scott AM, Bianco SR, Pettengill MJ, Meylemans H, Padilla M, Frazer-Abel AA, Akhtar N, Getzy DM, Wojcieszyn J, Breen M, Helfand SC, Modiano JF
JournalLaboratory investigation; a journal of technical methods and pathology
Volume84
Issue5
Pagination562-72
Date Published2004 May
ISSN0023-6837
KeywordsAnimals, Antigens, CD, Cell Adhesion, Cell Division, Cell Line, Tumor, Cell Movement, DNA, Neoplasm, Dog Diseases, Dogs, Endothelium, Vascular, Hemangiosarcoma, Humans, Models, Biological, Neovascularization, Pathologic, Ploidies, Vascular Endothelial Growth Factor A
Abstract

Hemangiosarcoma (HSA) is a common untreatable cancer of dogs that resembles human angiosarcoma. Detailed studies of these diseases have been historically hindered by the paucity of suitable reagents. Here, we show that expression of CD117 (c-Kit) can distinguish primitive (malignant) from mature (benign) proliferative endothelial lesions, and we describe eight independent cell lines derived from canine HSA explants. Endothelial origin was confirmed by sustained expression of surface CD105 (endoglin), CD146 (MUC18), and CD51/CD61 (alpha(v)beta(3) integrin). The cell lines showed anchorage-independent growth and were motile and invasive when cultured on a basement membrane matrix. They required endothelial growth factors for growth and survival, and they could be induced to form tubular structures resembling blood vessels when cultured under low calcium conditions. The formation of vessel-like structures was blocked by nicotine, and restored by FK506, suggesting that 'nuclear factor of activated T cells' activity prevents differentiation of these cells. In summary, these cell lines represent a unique and novel resource to improve our understanding of endothelial cell biology in general and canine HSA in particular.

Alternate JournalLab. Invest.