Summary
This study analyzed the transforming potential of murine viruses in organ cultures of mouse fetal condylar cartilage: Finkel-Biskis-Jinkins-Murine sarcoma virus (FBJ-MuSV) and Finkel-Biskis-Reilly-Murine sarcoma virus (FBR-MuSV). It was only the FBR-MuSV isolated from a radiation-induced osteosarcoma, that induced morphological changes as early as 24 hours following the infection. The latter manifested itself by a marked enlargement of the number of progenitor cells concomitant with an accumulation of spindle-like cells, giant cells, and pleomorphic cells along with large bone spicules and heavy mineralization of the remaining cartilage. The newly formed tissue synthesized type I collagen and revealed profound invasive characteristics. By day 7, FBR-MuSV-infected cultures acquired the appearance of an osteosarcomatouslike lesion. Electron microscopy examinations revealed that both the matrix and the osteogenic cells in the induced tumors differed markedly from that encountered in normal mammalian osseous tissue. To determine which cells within the condylar tissue served as the target for the FBR-MuSV, we used antibodies against viral P30 protein for an indirect immunoperoxidase reaction. The chondroprogenitor cells were the only ones that reacted positively for the virus-specific protein. Further, thein vitro-induced tumor was tumorigenic in syngeneic mice, hence, brought about the development of osteo-fibrosarcoma subcutaneously. By contrast to FBR-MuSV, the FBJ-MuSV did not elicit similar transformative effectsin vitro. Since both viruses possess the fos oncogene, it has been suggested that the unique tumorigenic potential of the FBR-MuSV may be linked to structural alterations in the fos oncogene product.
Similar content being viewed by others
References
Beug H, von Kirchbach A, Doderlein G, Conscience JF, Graf T (1979) Chicken hematopoietic cells transformed by seven strains of defective avian leukemia viruses display three distinct phenotypes of differentiation. Cell 18:375–390
Pierce JH, Aaronson SA (1982) Balo- and Harvey-murine sarcoma virus transformation of a novel lymphoid progenitor cell. J Exp Med 156:873–887
Silbermann M, Lewinson D, Gonen H, Lizarbe MA, von der Mark K (1983) In vitro transformation of chondroprogenitor cells into osteoblasts and the formation of new membrane bone. Anat Rec 206:373–383.
Silbermann M, Reddi H, Hand A, Leapman R (1986) In vitro differentiation of skeletoblasts and osteoblasts and the development of new bone. In: Ali Y (ed) Cell mediated calcification and matrix vesicles. Elsevier, Amsterdam, pp 285–290
Silbermann M (1983) Hormones and cartilage. In: Hall BK (ed) Cartilage, Vol. 2, Academic Press, New York, pp 327–368
Silbermann M, Maor G (1985) Receptor-mediated glucocorticoid inhibition of cell proliferation in mouse growth cartilage in vitro. Acta Endocrinol 108:343–350
Lewinson D, Silbermann M (1986) Parathyroid hormone stimulates proliferation of chondroprogenitor cells in vitro. calcif Tissue Int 38:155–162
Finkel MP, Biskis BO, Jinkins PB (1966) Virus induction of osteosarcoma in mice. Science 151:698–701
Finkel MP, Reilly CA, Biskis BO, Greco IL (1973) In: Price CHG, Ross FGM (eds) Bone-certain aspects of neoplasia. Butterworths, London, pp 353–364
Soehner RL, Dmochowski L (1969) Induction of bone tumors in rats and hamsters with murine sarcoma virus and their cell-free transmission. Nature 224:191–192
Nexo BA (1977) A plaque assay for murine leukemia virus using enzyme-coupled antibodies. Virology 77:849–852
Von der Mark H, von der Mark K, Gay S (1976) Immunofluorescence studies on differential collagen synthesis during development of chick embryo. Dev Biol 48:237–249
Franzen A, Heinegard D (1985) Isolation and characterization of two sialoproteins present only in bone calcified matrix. Biochem J 232:715–727
Majeska R, Nair BC, Rodan GA (1985) Glucocorticoid regulation of alkaline phosphatase in the osteoblastic osteosarcoma cell line ROS 17/2.8. Endocrinol 116:170–179
Weiss A, von der Mark K, Silbermann M (1986) A tissue culture system supporting cartilage cell differentiation, extracellular mineralization and subsequent bone formation using mouse condylar progenitor cells. Cell Diff 19:103–113
Silbermann M, Reddi H, Hand AR, leapman R, von der Mark K, Franzen A (in press) Cells with osteoblast characteristics arise from cartilage progenitor cells in organ culture of mandibular condyles. J Craniofacial Genet Dev Biol
Silbermann M, Tenenbaum H, Livne E, Leapman R, von der Mark K, Reddi H (in press) In vitro behaviour of fetal condylar cartilage in serum-free chemically supplemented medium. Bone
Fujinaga S, Poel WE, Domochowski L (1970) Light and electron microscope studies of osteosarcomas induced in rats and hamsters by Harvey and Moloney sarcoma virus. Cancer Res 30:1698–1708
Schmidt J, Livne E, Erfle V, Gossner W, Silbermann M (1986) The morphology of a de novo-induced osteosarcoma in an in vitro organ culture system. Cancer Res 46:3040–3098
Price CHG, Moore M, Jones DB (1972) A histopathological study of FBJ virus tumors and their relevance to murine and human osteosarcoma arising in bone. Br J Cancer 26:15–27
Van Breveven C, Enami S, Curran T, Verma IM (1984) FBR murine osteosarcoma virus II. Nucleotide sequence of the provirus reveals that the genome contains sequence acquired from two cellular genes. Virology 135:229–243
Curran T, MacConnell WP, van Straaten F, Verma IM (1983) Structure of the FBJ murine osteosarcoma virus genome: molecular cloning of its associated helper virus and the cellular homolog of the v-fos gene from mouse and human cells. Mol Cell Biol 3:914–921
Jenuwein T, Muller D, Curran T, Muller R (1985) Extended life-span and tumorigenicity of nonestablished mouse connective tissue cells transformed by the fos oncogene of FBR-MuSV. Cell 41:629–637
Greenberg ME, Ziff EB (1984) Stimulation of 3T3 cells induces transcription of the c-fos proto-oncogene. Nature 311:433–437
Muller R, Muller D, Guilbert L (1984) Differential expression of c-fos in hematopoietic cells: correlation with differentiation of monomyelocytic cells in vitro. EMBO J 3:1887–1890
Mitchell RL, Zokas L, Schreiber RD, Verma IM (1985) Rapid induction of the expression of proto-oncogene fos during human monocytic differentiation. Cell 40:209–217
Gonda TJ, Metcalf D (1984) Expression of myb, myc and fos proto-oncogenes during the differentiation of a murine myeloid leukemia. Nature 310:249–251
Muller R, Slamon DJ, Tremblay JM, Cline MJ, Verma IM (1982) Differential expression of cellular oncogenes during pre and postnatal development of the mouse. Nature 299:640–644
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Silbermann, M., Schmidt, J., Livne, E. et al. In vitro induction of osteosarcomalike lesion by transformation of differentiating skeletal precursor cells with FBR murine osteosarcoma virus. Calcif Tissue Int 41, 208–217 (1987). https://doi.org/10.1007/BF02555240
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF02555240