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Fate of Melanoma Cells Entering the Microcirculation: Over 80% Survive and Extravasate¹

Departments of Medical Biophysics [S. K., I. C. M., K. L., E. E. S., V. L. M., A. F. C., A. C. G.], Oncology [V. L. M., R. K., A. F. C.], Biochemistry [R. K.], and Microbiology and Immunology [V. L. M., M. G., A. F. C.], University of Western Ontario, London, Ontario N6A 5C1; London Regional Cancer Centre, London, Ontario N6A 4L6 [R. K., A. F. C.]; and John P. Robarts Research Institute, London, Ontario N6A 5K8 [A. C. G.], Canada

Metastasis is an inefficient process; only a few cancer cells are able to form tumors after being released into the circulation. We studied the fate of cancer cells after injection into the circulation, quantifying their survival and ability to extravasate by 1 day later. B16F10 cells, parental or transfectants overexpressing tissue inhibitor of metalloproteinases 1, were injected i.v. into chorioallantoic membrane of chick embryos and analyzed by intravital videomicroscopy. Cell survival was quantified in two ways: (a) 15-µm microspheres were injected with cancer cells, and proportions of viable cells to microspheres were compared before and after injection; and (b) individual cancer cells were monitored continuously for 0.5–8-h intervals covering the first 24 h. Both methods showed virtually no destruction of cells. Greater than 80% of injected cells survived and extravasated by 24 h, indicating that growth after extravasation is a key stage of metastatic control.

¹ This work was supported by National Cancer Institute of Canada Grant 3876 and Cancer Research Society Inc. S. K. is supported by a Scholarship from Fundação Coordenação de Aperfeiçoamento de Pessoal de Ensino Superior, Brazil. A. F. C. is a Career Scientist of the Ontario Cancer Treatment and Research Foundation. R. K. is a Medical Research Council Scholar.

² To whom requests for reprints should be addressed, at Department of Medical Biophysics, Health Sciences Center, University of Western Ontario, London, Ontario N6A 5C1, Canada.

Received 4/ 6/95. Accepted 5/ 5/95.

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