Canine malignant hemangiosarcoma as a model of primitive angiogenic endothelium

Susan P. Fosmire, Erin B. Dickerson, Allyson M. Scott, Stacie R. Bianco, Marilyn J. Pettengill, Heather Meylemans, Marcia Padilla, Ashley A. Frazer-Abel, Nasim Akhtar, David M. Getzy, John Wojcieszyn, Matthew Breen, Stuart C. Helfand, Jaime F. Modiano

Research output: Contribution to journalArticlepeer-review

81 Scopus citations

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 (αvβ3 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.

Original languageEnglish (US)
Pages (from-to)562-572
Number of pages11
JournalLaboratory Investigation
Volume84
Issue number5
DOIs
StatePublished - May 2004

Bibliographical note

Funding Information:
We gratefully acknowledge the assistance of the veterinarians and owners, respectively, who provided samples and who allowed participation of their dogs in this study. We wish to thank Karen Helm and Mike Ashton for assistance with flow cytometry, and Pepper Schedin for assistance with Matrigel assays and helpful suggestions. Supported in part by Grant 2025 from the AKC Canine Health Foundation to SCH, Grant 0791 from the Smokeless Tobacco Research Council, a grant from the Philip Morris External Research Program, and Grant 1 R55 CA86432 from the NCI to JFM, and by a grant from the Monfort Family Foundation to the University of Colorado Cancer Center. Canine molecular cytogenetics research at NCSU is supported by funds from the AKC Canine Health Foundation to MB. SRB and HM were supported in part by an educational grant (R25 CA49981) from the NCI. The University of Colorado Cancer Center Flow Cytometry Core is supported by Grant 5 P30 CA46934 from the NCI.

Keywords

  • Angiogenesis
  • Angiosarcoma
  • CD117
  • Canine
  • Endothelial cells
  • NFAT
  • Nicotine

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