Reproducible generation of autonomous malignant sublines from non-tumorogenic murine interleukin 3-dependent mast cell lines.

Murine interleukin 3 (IL-3)-dependent permanent mast cell lines derived from normal mouse bone marrow were established using pokeweed mitogen-stimulated spleen cell conditioned medium (SCM) as a source of IL-3. When propagated continuously in media containing a high concentration of IL-3 (20% SCM or 20 U/ml murine recombinant IL-3 (rIL-3], all the cell lines remained strictly factor-dependent in vitro and non-tumorogenic in vivo. However, we were able to reproducibly generate autonomous sublines from cultures supplemented with low amounts of IL-3 (1% SCM or 2 U/ml rIL-3). Abrogation of exogeneous growth factor dependency was always associated with neoplastic transformation. In newly generated autonomous sublines an autocrine mechanism of growth regulation was evident in vitro.