Metastatic conversion of factor-dependent lung fibroblasts (CCL39) requires over-expression of oncogenes which induce high rate of autonomous replication.

Several classes of oncogenes were tested for their ability to confer cellular growth autonomy and the metastatic phenotype on CCL39 lung fibroblasts. v-sis as well as highly but not weakly expressed activated ras, v-fps and myc genes were susceptible to relieve CCL39 cells from their dependence on exogenous growth factors. However, based on growth rate estimations, ras and fps cells divided 2 to 3 times more rapidly than myc and sis cells in serum-free medium. All ras and fps cells produced pulmonary metastases in 60-100% of young nude mice, following subcutaneous or intravenous injection. Acquisition of factor-independent growth during in vivo passage was demonstrated in two instances. Animals developed either no or sporadic metastases after implantation of transfected cells expressing v-sis, normal Ha-ras, myc or no foreign oncogene. The results are consistent with the notion that the rate at which tumor cells can proliferate independently from growth factor stimulation is a good predictor of their metastatic potential. Oncogenes such as activated ras and fps appear more efficient than myc and sis to induce the metastatic conversion of preneoplastic CCL39 cells and to abrogate Go-arrest controls of division.