1. ¹AMC Cancer Research Center and Integrated Department of Immunology, University of Colorado Health Sciences Center, Denver, CO, USA
2. ²Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI, USA
3. ³Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA
4. ⁴Idexx Veterinary Services, Broomfield, CO, USA
5. ⁵IHC Services, Smithville, TX, USA
6. ⁶University of Wisconsin Comprehensive Cancer Center, Madison, WI, USA
7. ⁷University of Colorado Cancer Center, Denver, CO, USA

Correspondence: JF Modiano, AMC Cancer Research Center, 1600 Pierce Street, Denver, CO 80214, USA. E-mail: modianoj@amc.org

Received 21 November 2003; Revised 21 January 2004; Accepted 21 January 2004; Published online 5 April 2004.

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 (_v3 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.