The purpose of this study was to explore further an in vitro system to evaluate the interaction between cancer cells and normal cells. In the tumor-induced marrow cytotoxicity assay, 59Fe- and 51Cr-labeled bone marrow cells were cocultured with different types of cancer cells. Following an 18-hr incubation, the mixed-cell cultures were centrifuged, and the 59Fe and 51Cr in the supernatant solution (released by cell death) were compared to the total radio-activity and expressed as a release index. In the presence of cocultured Novikoff or Yoshida hepatoma cells, the release of isotopes by rat bone marrow cells increased linearly with increasing tumor cell concentrations. With equal numbers (1 × 107/ml) of cancer cells and 59Fe-labeled marrow cells, the marrow release indices with Novikoff and Yoshida hepatoma cells were 36.1 ± 0.1% (S.D.) and 38.6 ± 1.0%, respectively, as compared to a spontaneous marrow release index of 27.4 ± 0.1%. Similar results were obtained when mouse teratocarcinoma cells were cocultured with syngeneic mouse marrow cells. Transformed rat fibroblasts were also able to induce the cytolysis of normal rat marrow or fibroblast target cells. Normal rat spleen cells, blood lymphocytes and fibroblasts were inactive as effector cells in the tumor-induced marrow cytotoxicity assay. Activated macrophages which have demonstrated a cytolytic capacity in other assay systems were able to induce marrow cell lysis. However, phytohemagglutinin-stimulated lymphocytes were not cytotoxic to normal marrow.
These experiments suggest that the capacity to induce the release of 59Fe and 51Cr from labeled marrow cells is a common property of transplanted cancer cells. We propose that the tumor-induced marrow cytotoxicity assay will be a useful experimental technique to enhance our understanding of the mechanisms of cancer invasion.
This research was supported by grant funds from the Veterans Administration Medical Center (MRIS 9939) and the National Cancer Institute (CA 15629).