Metastasis-suppressed C8161 melanoma cells arrest in lung but fail to proliferate

The incidence of melanoma continues to increase at a rapid rate. As for mos t cancers, it is melanoma metastases, rather than the primary malignancy, t hat is the principal cause of death. We previously showed that the introduc tion of a normal copy of chromosome 6 into the metastatic human melanoma ce ll line C8161 suppresses metastasis at a step subsequent to tumor cells ent ering the bloodstream. To better define the step(s) in metastasis blocked b y the addition of chromosome 6 we engineered cells that constitutively expr ess green fluorescent protein (GFP). When these tagged, chromosome 6 hybrid cells were injected intravenously into athymic mice, grossly detectable me tastases did not form. However, fluorescence microscopy revealed micro-meta stases (single cells or clusters of < 10 cells) in the lungs, suggesting th at these cells lodged in the lungs but failed to proliferate. Cells isolate d from lung up to 60 days post-injection grew in culture and/or formed tumo rs when injected into the skin, indicating that they were still viable, but dormant. This result implies that the gene(s) on chromosome 6 interfere sp ecifically with growth regulatory response in the lung, but not in the skin . Thus, the gene(s) responsible for metastasis suppression represents a new class of metastasis inhibitors acting at the final stages of the metastati c cascade - that is, affecting the ability of the cells to survive and prol iferate at a specific secondary site.