A spontaneous murine melanoma lung metastasis comprised of host x tumor hybrids

Cells from a lung metastasis, arising from Cloudman S91 melanoma cells impl anted s.c. in the tail of a BALB/c nu/nu mouse, were comprised chiefly of h ost x tumor hybrids. These lung metastasis cells showed: (a) 30-40% increas ed DNA content; (b) resistance to 10(-4) M hypoxanthine, 4 x 10(-7) M amino pterin, and 1.6 x 10(-5) M thymidine (HAT) + G418; and (c) the presence in genomic DNA of genes for both wt and albino tyrosinase, reflecting the DBA/ 2J (Cloudman S91) and BALB/c mouse genotypes, respectively. Individual clon es of lung metastasis cells expressed enhanced pigmentation, motility, and responsiveness to MSH/IBMX, a behavior similar to that recently reported fo r artificially generated melanoma x macrophage fusion hybrids. These simila rities suggested that the host fusion partner generating the Lung metastasi s hybrids might have been a macrophage, although formal proof for this was not possible. The results provide the first direct evidence that host x tum or hybridization could serve as an initiating mechanism for melanoma metast asis.