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

Cancer Metastasis Program, Michigan Cancer Foundation, Detroit, Michigan 48201

The in vitro motility of B16-F1 melanoma cells is enhanced by incubation with a monoclonal antibody against gp78, previously characterized 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 high- and 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 high-metastatic clones. Priming of cells by preventing internalization of gp78-antibody complexes by pertussis toxin resulted in a marked enhancement of pulmonary metastases by the treated cells which was directly correlated 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.

¹ This work was supported by a grant to A. R. from the Paul Zuckerman Support Foundation for Cancer Research.

² Present address: Department of Orthopaedic Surgery, Gunma University School of Medicine, Maebashi, Gunma 371, Japan.

³ Present address: Department of Cell Biology and Anatomy, Cornell University Medical College, New York, NY 10021.

⁴ To whom requests for reprints should be addressed, at Michigan Cancer Foundation, Meyer L. Prentis Cancer Center, 110 E. Warren Avenue, Detroit, MI 48201.

Received 7/16/90. Accepted 3/ 5/91.

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