Differences in cell surface characteristics between glucocorticoid-sensitive and -resistant mouse lymphomas.

SUMMARY The presence or absence of anionic sites on the cell surface was studied in corticoid-sensitive (CS) and-resistant (CR) P1798 lymphosarcoma as well as in CS and CR 6C3HED lymphoma by reaction with the cationic stain Alcian Blue 8GX. Examination by electron microscopy revealed dye complexes on cell surfaces of all CS tumors. Reaction product could be observed as an electron-dense coat of variable thickness on the outer leaflet of the cell membrane, indicating the presence of anionic sites. A small number of cells in CS populations lacked coat material. Cells from both CR tumors showed no or few scattered electron-opaque complexes on their surfaces, with the exception of a small number of cells that had a continuous cell coat. Possible charge-related differences in ultrastructural arrangement of cells in the intact tumor tissue and cell surface morphology of individual cells were investigated in P1798-CS and-CR. CR cells were frequently observed to adhere to each other by cytoplasmic bridges, whereas CS cells generally showed a looser arrange ment with fewer contact sites. Scanning electron microscopy revealed smooth and moderately viulous surfaces in both P1798-CS and-CR cell preparations. Approximately 45% of P1798-CR cells showed a prominent single protrusion, resulting in a pear or mushroom shape. Relatively few (11%) of such irregular patterns were seen in P1798-CS cell preparations. These observations suggest that corticoid sensi tivity of lymphoid tumors is related to variations in cell membrane properties that are determined by negative surface charge. INTRODUCFION The cytolytic effect of glucocorticoids on lymphoid tissues forms the basis for the use of these hormones in the treatment of malignant lymphoid tumors. However, the therapeutic usefulness of glucocorticoids is often hampered by the presence of steroid-resistant cell lines. Initial cytotoxic events in corticoid-responsive tissues appear to be related to impaired transport phenomena, such as inhibition of glucose (12, 16), amino acid (1 7), and nucleoside transport (23), which are preceded by the formation of specific hormone receptor complexes and by 1 or more steps involving macromolecular synthesis (1, 12). In our laboratory, solid P1798-CR5 tumors have been observed to be noticeably firmer and were consistently found to yield fewer cells (upon teasing or gentle mincing) than did P1798-CS tumors. In this study, possible differences in cell surface charge were investigated in CS and CR P1798 and 6C3HED lymphosarcoma cell lines by electron microscopy. The presence or absence of anionic sites on the surface of the cell …