Interactions among clonal subpopulations affect stability of the metastatic phenotype in polyclonal populations of B16 melanoma cells.

Analysis of the metastatic properties of clones isolated from mouse B16 melanoma cell lines (B16-F1 and F10) shows extensive cellular heterogeneity and the presence of subpopulations that have widely differing metastatic abilities. This pattern of metastatic heterogeneity is maintained during serial passage in vitro and in vivo. In contrast, even a short serial passage of individual clones isolated from these heterogeneous parent lines results in rapid emergence of variant subclones that have different metastatic properties. If several clones are mixed and cocultivated, this instability is not expressed. These data suggest that, in polyclonal populations, the various clonal subpopulations somehow interact with one another to "stabilize" their relative proportions within the population. Restriction of clonal diversity by selective killing of the majority of clones in a polyclonal population eliminates the stabilizing restraints and stimulates rapid emergence of new subpopulations to create heterogeneous populations containing a new panel of phenotypically diverse subpopulations that then reach stable proportions until the next selection pressure(s) is encountered.