IGF-1 receptor contributes to the malignant phenotype in human and canine osteosarcoma.
To further define the role of insulin-like growth factor-1 (IGF-1) and its receptor (IGF-1R) in osteosarcoma (OS), human OS cell lines with low (SAOS-2) and high (SAOS-LM2) metastatic potential and three canine OS-derived cell lines were studied. Cell lines were evaluated for: IGF-1R expression; expression of IGF binding proteins (IGFBPs); effect of IGF-1 on tumor cell growth, invasion, expression of urokinase plasminogen activator (uPA), and soluble uPA receptor (suPAR), and; ectopic and orthotopic tumorigenicity of the canine OS cells in athymic mice. All cell lines exhibited steady-state mRNA expression of IGF-1R. The SAOS-2 and SAOS-LM2 cells expressed 9,138 and 10,234 cell-associated binding sites, respectively. Canine OS cells expressed from 1,728 to 3,883 binding sites. Two IGF-1-treated cell lines displayed enhanced proliferation. Two cell lines formed colonies in semisolid media, and IGF-1 increased colony number. Matrigel invasion was enhanced in one cell line following IGF-1 treatment. uPA and suPAR were unchanged in SAOS-2 and SAOS-LM2 cells following IGF-1 treatment, but the highly metastatic OS line SAOS-LM2 expressed five times more suPAR and displayed enhanced invasion compared to the parental, low metastatic SAOS-2. IGFBP-5 was detected in four of five cell lines, and IGFBP-3 was detected in two canine OS cell lines. Two canine OS lines were tumorigenic, and one metastasized spontaneously. In conclusion, OS cells express IGF-1R, which can contribute to their growth and invasion. There is suggestive evidence that increasing receptor number may contribute to in vivo tumorigenesis. Additional studies are needed to determine how IGF-1/IGF-1R interactions contribute to the malignant phenotype of OS.
MacEwen
E Gregory
EG
Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.
Pastor
Josep
J
Kutzke
Jonathan
J
Tsan
Rachel
R
Kurzman
Ilene D
ID
Thamm
Douglas H
DH
Wilson
Mike
M
Radinsky
Robert
R
D000818:Animals; D001859:Bone Neoplasms / Q000378:metabolism* / Q000473:pathology*; D002460:Cell Line; D004285:Dogs; D015870:Gene Expression; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008168:Lung / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D012516:Osteosarcoma / Q000378:metabolism* / Q000556:secondary*; D011485:Protein Binding; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000378:metabolism*; D014183:Transplantation, Heterologous; D014568:Urokinase-Type Plasminogen Activator / Q000032:analysis
D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1; D014568:Urokinase-Type Plasminogen Activator