Comparison of the Metastatic Properties of B16 Melanoma Clones Isolated from Cultured Cell Lines, Subcutaneous Tumors, and Individual Lung Métastases

Tumors produced by s.c. injection of uncloned B16 mela noma cell lines contain clonal tumor cell subpopulations with widely differing metastatic properties, including clones that are nonmetastatic. Similar metastatic heterogeneity exists in clones isolated from the same cell lines cultured in vitro. In B16 melanoma sublines (B16-BL6, B16-BV8, and B16-BP8) se lected for enhanced invasive and metastatic behavior, the proportion of clones with high metastatic capacity is increased relative to the parent cell line. The cellular composition of métastasesproduced by s.c. or i.v. injection of the uncloned parent cell line has also been examined. Some métastasesare populated by clones with indistinguishable metastatic proper ties (intralesional clonal homogeneity) while others yield clones with different metastatic properties (intralesional clonal heter ogeneity). The range of clonal diversity in heterogeneous mé tastases is, however, substantially less than in the parent line. The number of métastasesyielding clones with heterogeneous metastatic phenotypes is higher for "spontaneous" métastases arising from s.c. tumors than in "experimental" métastases produced by i.v. injection of single-cell suspensions. Studies using B16 cells bearing specific biochemical markers indicate that clonally homogeneous métastasesare of monoclonal ori gin and that métastases populated by clones with heteroge neous metastatic phenotypes are of polyclonal origin.