In vitro induction of osteosarcomalike lesion by transformation of differentiating skeletal precursor cells with FBR murine osteosarcoma virus

Abstract

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, the in 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 effects in 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.