Interleukin-12 inhibits tumor growth in a novel angiogenesis canine hemangiosarcoma xenograft model.
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 alpha(v)beta(3) 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.
Akhtar
Nasim
N
Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI 53706, USA.
Padilla
Marcia L
ML
Dickerson
Erin B
EB
Steinberg
Howard
H
Breen
Matthew
M
Auerbach
Robert
R
Helfand
Stuart C
SC
D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D002448:Cell Adhesion; D002455:Cell Division; D016510:Corneal Neovascularization / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D004285:Dogs; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D005434:Flow Cytometry; D006133:Growth Substances / Q000378:metabolism; D006394:Hemangiosarcoma / Q000098:blood supply* / Q000473:pathology; D018664:Interleukin-12 / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012983:Soft Tissue Neoplasms / Q000098:blood supply* / Q000473:pathology; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D014408:Biomarkers, Tumor; D016207:Cytokines; D006133:Growth Substances; D018664:Interleukin-12