STUDIES ON PROTEIN UPTAKE BY ISOLATED TUMOR CELLS : I. Electron Microscopic Evidence of Ferritin Uptake by Ehrlich Ascites Tumor Cells

Ferritin, added to the incubation medium of ascites tumor cells, was used as an electron microscopic marker to study the uptake of large protein molecules by morphologically intact cells. A definite uptake could be detected after 1 hour of incubation in Tyrode bicarbonate solution containing 0.04 to 13.3 mg ferritin/ml. Ferritin was found in a variety of membrane-surrounded structures, suggesting that pinocytesis and related membrane movements are occurring under physiological conditions and can account for the penetration of intact macromolecules into isolated tumor cells. Supplementation of the medium with serum albumin (33 mg/ml) increased the average amount of ferritin per cell and per pinocytotic structure. Ferritin was strongly adsorbed by fragments of lysed cells, which were readily taken up by intact cells. Besides its role as carrier, this debris appeared to stimulate membrane movements. Only rare examples were found to suggest the release of ferritin from the pinocytotic structures into the cytoplasm. Thus, the disintegration of such structures cannot be considered an obvious step towards a rapid metabolic utilization of protein by the cell. Particles of colloidal gold presented to the cell under the same conditions were not taken up to any significant extent, thus providing good evidence for a selective ingestion of particles of comparable sizes.