Predominance of the metastatic phenotype in somatic cell hybrids of the K-1735 murine melanoma.

ABSTRACT

The purpose of these studies was to determine whether the metastatic phenotype will dominate when metastatic and nonmetastatic clones of the K-1735 mouse melanoma are hybridized by somatic cell fusion. Three nonmetastatic and three metastatic clones were transfected with DNA from plasmids pSV2neo or pSV2hygro, which confer resistance to the drugs neomycin or hygromycin, respectively. The metastatic properties of the six clones were not altered by these transfections. The tumorigenicity and metastatic capacity of cell hybrids formed by somatic cell fusion of nonmetastatic and metastatic clones were examined. To do so, near-tetraploid hybrids containing a nearly complete chromosomal complement from both parental cells were injected i.v. into syngeneic mice, and the number of metastatic nodules in the lung was determined at 45 days or when the mice became moribund. Seven of nine hybrids produced from the fusion of metastatic and nonmetastatic clones exhibited a highly metastatic phenotype, although in most cases the metastatic potential of the hybrids was lower than that of the metastatic parent cells. Very similar results were obtained in athymic nude mice. The metastatic potential of the hybrids was directly correlated with their growth in the subcutis of nude mice. These results indicate that the metastatic capacity of K-1735 cells predominates in somatic cell hybrids between nonmetastatic and metastatic cells. When fusion of nonmetastatic and metastatic cells yields a hybrid with nonmetastatic properties, it may be due to suppression of growth.