MELANOMA X MACROPHAGE HYBRIDS WITH ENHANCED METASTATIC POTENTIAL

Studies were conducted on the hypothesis that melanoma metastasis migh t be initiated through the generation of hybrids comprised of cells of the primacy tumor and tumor-infiltrating leukocytes. Fusion hybrids w ere generated in vitro between weakly metastatic Cloudman S91 mouse me lanoma cells and normal mouse or human macrophages, Hybrids were impla nted s.c. in the tail and mice were monitored for metastases, Controls included parental S91 cells, autologous S91 x S91 hybrids, and B16F10 melanoma cells. Of 35 hybrids tested, most were more aggressive than the parental melanoma cells, producing metastases sooner and in more m ice. A striking characteristic was heterogeneity amongst hybrids, with some lines producing no metastases and others producing metastases in up to 80% of mice. With few exceptions, hybrids with the highest meta static potential also had the highest basal melanin content whereas th ose with the lowest metastatic potential were basally amelanotic, as w ere the parental melanoma cells. A spontaneous in vivo supermelanotic hybrid between an S91 tumor cell and DBA/2J host cell was one of the m ost metastatic lines, Hybrids with the highest metastatic potential al so exhibited markedly higher chemotaxis to fibroblast-conditioned medi a. Histologically, the metastatic hybrids demonstrated vascular invasi on and spread to distant organs similar to that of metastatic melanoma s in mice and humans. Thus previous findings of enhanced metastasis in leukocyte x lymphoma hybrids can now be extended to include leukocyte x melanoma hybrids. Whether such hybridization is a natural cause of metastasis in vivo remains to be determined; however the fusion hybrid s with genetically-matched parents described herein so closely resembl ed naturally-occurring metastatic melanoma cells that they could serve as useful new models for studies of this complex and deadly phenomeno n. (C) 1998 Lippincott-Raven Publishers.