Inducibility of neoplastic transformation by Fujinami sarcoma virus in an in vitro chick embryo model for osteosarcoma: (i) effect of differentiation and (ii) investigation for in vivo growth potential in athymic mice.
We have described previously a novel in vitro model for the study of osteosarcoma. In this system, chick periosteal explants (CEP) transformed by the P140gag-fps oncoprotein of Fujinami avian sarcoma virus (FSV) exhibit biochemical and histological manifestations characteristic of osteosarcoma. In the present study, a hypothesis suggesting that more differentiated bone cells may resist FSV-induced oncogene changes was tested. In one set of experiments, CEP cultures were pretreated with a high dose of dexamethasone (10(-7) M), a bone cell differentiating agent, prior to FSV infection. In another experiment, CEP explants were allowed to grow and thus differentiate for various lengths of time in culture prior to infection with FSV. Another goal of this study was to show that FSV-transformed cultures were tumorigenic in nude mice. In experiments focusing on differentiation and FSV-transformation, it was found that groups that had been infected at stages where osteogenic differentiation had been induced or allowed to occur, exhibited significantly decreased values for biochemical parameters associated with osteosarcomatous transformation. Specifically, these parameters were alkaline and acid phosphatase activity, protein content, [3H]thymidine incorporation, mineral profile, and acidification of culture media. Furthermore, osteosarcomatous histopathological features were more prominent in cultures subjected to FSV infection prior to differentiation. These findings indicate that differentiated osteogenic cells are less susceptible to oncogene-mediated transformation than their progenitors. The tumorigenic potential of some CEP cultures transformed in vitro with FSV was examined by transplantation into athymic mice. FSV-transformed CEP cultures xenografted subcutaneously exhibited tumor formation, whereas xenografts of uninfected cultures did not grow or were completely resorbed. This demonstrates that FSV-transformed cultures are tumorigenic, and confirms that this model system is useful for the investigation of the mechanisms governing the development of osteosarcoma in vitro.
Cogliano
A
A
Mount Sinai Hospital Research Institute, University of Toronto, Ontario, Canada.
Birek
C
C
Tenenbaum
H C
HC
D000818:Animals; D001358:Avian Sarcoma Viruses / Q000254:growth & development*; D016025:Bone Transplantation / Q000502:physiology; D001842:Bone and Bones / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002472:Cell Transformation, Viral / Q000502:physiology*; D002478:Cells, Cultured; D002642:Chick Embryo; D003907:Dexamethasone / Q000494:pharmacology; D004195:Disease Models, Animal; D051379:Mice; D008819:Mice, Nude; D008854:Microscopy, Electron; D012516:Osteosarcoma / Q000503:physiopathology*; D014183:Transplantation, Heterologous; D014775:Virus Activation / Q000502:physiology*
D003907:Dexamethasone