Noncorrelation between implantation and growth of tumor cells for their final metastatic efficiency

We have measured the relative contribution of implantation and focal growth metastatic phenomena on the hepatic colonization process of intrasplenically injected B16 melanoma or Lewis lung carcinoma (LLC) tumor cells. To do this, an experimental variation of the parental tumor cell phenotype (seed factor) was performed by a selection of 10 times passaged hepatic-metastasizing tumor cells and changes in biological features of host tissue (soil) were induced following the treatment of the mice with ciclosporin, Thymostimulin, Bleomycin, silica particles or 17 alpha-ethynylestradiol prior to tumor injection. Implantation efficiency of selected variants was highly increased but, while the focal metastatic growth efficiency did not vary in LLC variants, in selected B16 melanoma cells it was clearly higher. In all the pretreated animals final metastatic volume varied with respect to the controls. In some mice, implantation efficiency was increased but this effect did not always determine later increments in the final metastatic volume. In other mice, focal growth of metastases was reduced with respect to the controls without correlative reductions in the final metastatic volume. In general, changes of final metastatic volume in the liver were mostly dependent upon the ability of tumor cells to successfully implant. Thus, final metastatic volume seems to depend on the sum of two relatively independent colonization phenomena: tumor cell implantation and focal growth of metastases.