Transforming factors in human sarcoma cells in tissue culture

Experimental data are presented which demomstrate the existence of a transmissible factor(s) in the majority of samples of leukemic bone marrow. This factor(s) is associated with the presence of a cytoplasmic antigen which can be detected by fixed immunofluorescence test with sera of patients with osteosarcoma, leukemia and some apparently normal individuals. Cultures of leukemic bone marrow carrying this factor(s) also form multinucleated cells when exposed to RD114 virus or cels. This factor(s) is transmitted into susceptible whole human embryo cells by cell-free culture fluid. Appearance of the new antigen can be detected by fixed immunofluorescence test about 6 weeks after transmission. Cultures showing the new antigen also form multinucleated cells following co-cultivation with RD114 virus or cells. Co-cultures of human osteosarcoma cells and leukemic bone marrow cells undergo morphologic as well as antigen changes after a long period of time (at least 3 months). Cell line fluids from these cultures contain a factor which induces in recipient whole human embryo cultures both the new antigen and morphological alterations resembling those observed in the co-cultures. Cell-free fluids from leukemic bone marrow and sarcoma cultures as well as from short-term co-cultures have failed to produce morphological alterations in whole human embryo cells. Extensive electron microscope studies carried out at different stages of the experiments have failed to reveal the presence of viral particles. The morphological changes resemble those induced in susceptible cells by sarcoma viruses. The described factor(s) may conceivably represent subviral components capable of biological activity. While suggestive of viral involvement in human sarcoma of bone and soft tissues, there is no definite proof of viruses being the causative agent(s) of human sarcoma. Present evidence provides only a basis for search of additional ways of treatment of human sarcoma to those of surgery and radiotherapy. Present treatment consists of chemotherapy as adjuvant treatment directed against viral markers represented by enzymes, nucleic acids and proteins of possible viral origin, resembling those already known to be present in animal bone and soft tissue sarcomas. However tenuous the contention of the possiblity of viral involvement in human osteosarcoma may appear, adjuvant therapy directed against viral markers warrants the attention of orthopedic surgeons and other clinicians.