Changes in clonal composition during in vivo growth of mixed subpopulations derived from the murine K-1735 melanoma

We determined the conditions necessary for a metastatic clone of the K-1735 melanoma to become dominant over nonmetastatic clones. Different mixtures of metastatic and low or nonmetastatic cells which can be identified by detailed karyotype analysis were injected into the subcutis of syngeneic C₃H/HeN and allogeneic nude mice. Early (small) and late (large) subcutaneous tumors were removed and enzymatically dissociated, and cell cultures were established. The clonal composition of the cultures was determined by cytogenetic analysis. In syngeneic mice, dominance by the metastatic clone occurred only when the initial inoculum consisted of at least 5% metastatic and 95% nonmetastatic cells. In nude mice, dominance by the metastatic clone occurred even with an inoculum of 1% metastatic and 99% nonmetastatic cells, syggesting that host immunity plays a major role in this tumor system.