title: Canine malignant hemangiosarcoma as a model of primitive angiogenic endothelium.
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.
authors.affiliation: AMC Cancer Research Center and Integrated Department of Immunology, University of Colorado Health Sciences Center, Denver, 80214, USA.
authors.forename: Susan P
authors.initials: SP
authors.lastname: Fosmire
authors.forename: Erin B
authors.initials: EB
authors.lastname: Dickerson
authors.forename: Allyson M
authors.initials: AM
authors.lastname: Scott
authors.forename: Stacie R
authors.initials: SR
authors.lastname: Bianco
authors.forename: Marilyn J
authors.initials: MJ
authors.lastname: Pettengill
authors.forename: Heather
authors.initials: H
authors.lastname: Meylemans
authors.forename: Marcia
authors.initials: M
authors.lastname: Padilla
authors.forename: Ashley A
authors.initials: AA
authors.lastname: Frazer-Abel
authors.forename: Nasim
authors.initials: N
authors.lastname: Akhtar
authors.forename: David M
authors.initials: DM
authors.lastname: Getzy
authors.forename: John
authors.initials: J
authors.lastname: Wojcieszyn
authors.forename: Matthew
authors.initials: M
authors.lastname: Breen
authors.forename: Stuart C
authors.initials: SC
authors.lastname: Helfand
authors.forename: Jaime F
authors.initials: JF
authors.lastname: Modiano
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D002448:Cell Adhesion; D002455:Cell Division; D045744:Cell Line, Tumor; D002465:Cell Movement; D004273:DNA, Neoplasm / Q000032:analysis / Q000235:genetics; D004283:Dog Diseases / Q000473:pathology* / Q000503:physiopathology; D004285:Dogs; D004730:Endothelium, Vascular / Q000473:pathology; D006394:Hemangiosarcoma / Q000098:blood supply / Q000473:pathology / Q000503:physiopathology / Q000662:veterinary*; D006801:Humans; D008954:Models, Biological; D009389:Neovascularization, Pathologic; D011003:Ploidies; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D004273:DNA, Neoplasm; D042461:Vascular Endothelial Growth Factor A