FATE OF MELANOMA-CELLS ENTERING THE MICROCIRCULATION - OVER 80-PERCENT SURVIVE AND EXTRAVASATE

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, quantif ying their survival and ability to extravasate by 1 day later. B16F10 cells, parental or transfectants overexpressing tissue inhibitor of me talloproteinases 1, were injected i.v. into chorioallantoic membrane o f chick embryos and analyzed by intravital videomicroscopy. Cell survi val was quantified in two ways: (a) 15-mu m microspheres were injected with cancer cells, and proportions of viable cells to microspheres we re compared before and after injection; and (b) individual cancer cell s 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, indicati ng that growth after extravasation is a key stage of metastatic contro l.