The Relationship between Motility Factor Receptor Internalizaron and the Lung Colonization Capacity of Murine Melanoma Cells1

The in vitro motility of B16-F1 melanoma cells is enhanced by incubation with a monoclonal antibody against gp78, previously charac terized as a motility factor receptor. This antibody was used to study the relationship between motility stimulation in vitro and metastatic ability in vivo in the B16-F1 and K-1735 murine melanoma systems. While both highand low-metastatic variants exhibited enhanced in vitro motility in response to the anti-gp78 monoclonal antibody, only the high-metastatic cells exhibited an increased metastatic ability. Surface immunofluorescence of low-metastatic cells was distributed more diffusely compared to a highly localized patching of gp78 on high-metastatic cells, suggesting that the directed endocytosis of gp78 to form a single leading edge is related to the metastatic ability of a cell, while fluorescence-activated cell sorter analysis revealed decreased gp78 surface expression in highmetastatic clones. Priming of cells by preventing internalization of gp78antibody complexes by pertussis toxin resulted in a marked enhancement of pulmonary métastasesby the treated cells which was directly corre lated with decreased surface expression of gp78 following washout of pertussis toxin. These results suggest that cell motility induced by motility factor receptor occupancy may play a role in the process of metastasis and that the ligand-receptor complex internalization from the cell surface is involved in control of cell kinesis during metastasis.