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IGF‐1 receptor contributes to the malignant phenotype in human and canine osteosarcoma
Author(s) -
MacEwen E. Gregory,
Pastor Josep,
Kutzke Jonathan,
Tsan Rachel,
Kurzman Ilene D.,
Thamm Douglas H.,
Wilson Mike,
Radinsky Robert
Publication year - 2004
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.20046
Subject(s) - cell culture , urokinase receptor , matrigel , cancer research , osteosarcoma , cell growth , receptor , supar , biology , ectopic expression , cell , growth factor , plasminogen activator , microbiology and biotechnology , endocrinology , medicine , angiogenesis , genetics
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. © 2004 Wiley‐Liss, Inc.