Comparison of the metastatic properties of B16 melanoma clones isolated from cultured cell lines, subcutaneous tumors, and individual lung metastases.

Tumors produced by s.c. injection of uncloned B16 melanoma 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) selected 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 metastases produced by s.c. or i.v. injection of the uncloned parent cell line has also been examined. Some metastases are populated by clones with indistinguishable metastatic properties (intralesional clonal homogeneity) while others yield clones with different metastatic properties (intralesional clonal heterogeneity). The range of clonal diversity in heterogeneous metastases is, however, substantially less than in the parent line. The number of metastases yielding clones with heterogeneous metastatic phenotypes is higher for "spontaneous" metastases arising from s.c. tumors than in "experimental" metastases produced by i.v. injection of single-cell suspensions. Studies using B16 cells bearing specific biochemical markers indicate that clonally homogeneous metastases are of monoclonal origin and that metastases populated by clones with heterogeneous metastatic phenotypes are of polyclonal origin.