Interleukin-12 Inhibits Tumor Growth in a Novel Angiogenesis Canine Hemangiosarcoma Xenograft Model

Nasim Akhtar, Marcia L. Padilla, Erin B. Dickerson, Howard Steinberg, Matthew Breen, Robert Auerbach, Stuart C. Helfand

Research output: Contribution to journalArticlepeer-review

63 Scopus citations

Abstract

We established a canine hemangiosarcoma cell line derived from malignant endothelial cells comprising a spontaneous tumor in a dog to provide a renewable source of endothelial cells for studies of angiogenesis in malignancy. Pieces of the hemangiosarcoma biopsy were engrafted subcutaneously in a bg/nu/XID mouse allowing the tumor cells to expand in vivo. A cell line, SB-HSA, was derived from the xenograft. SB-HSA cells expressed vascular endothelial growth factor (VEGF) receptors 1 and 2, CD31, CD146, and α vβ3 integrin, and produced several growth factors and cytokines, including VEGF, basic fibroblast growth factor, and interleukin (IL)-8 that are stimulatory to endothelial cell growth. These results indicated that the cells recapitulated features of mitotically activated endothelia. In vivo, SB-HSA cells stimulated robust angiogenic responses in mice and formed tumor masses composed of aberrant vascular channels in immunocompromised mice providing novel opportunities for investigating the effectiveness of antiangiogenic agents. Using this model, we determined that IL-12, a cytokine with both immunostimulatory and antiangiogenic effects, suppressed angiogenesis induced by, and tumor growth of, SB-HSA cells. The endothelial cell model we have described offers unique opportunities to pursue further investigations with IL-12, as well as other antiangiogenic approaches in cancer therapy.

Original languageEnglish (US)
Pages (from-to)106-116
Number of pages11
JournalNeoplasia
Volume6
Issue number2
DOIs
StatePublished - 2004
Externally publishedYes

Bibliographical note

Funding Information:
Address all correspondence to: Stuart C. Helfand, School of Veterinary Medicine, University of Wisconsin, 2015 Linden Drive, Madison, WI 53706-1102, USA. E-mail: helfands@svm.vetmed.wisc.edu 1Supported by National Institutes of Health grants CA86264, CA14520, and P30 CA14520-29, and AKC/CHF grant 2025 (S.C.H.). 2Equal contribution. Received 15 September 2003; Revised 1 December 2003; Accepted 3 December 2003.

Keywords

  • Angiogenesis
  • Cytokine
  • Dog
  • Endothelial cell
  • Malignant

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