Oxygen consumption by tumor cells during membrane vesicle shedding

Abstract

The incubation of mastocytoma P815 cells at low temperature (0 °C/1–2 hr), with a subsequent shift to ≥20 °C results in the formation and shedding of membrane vesicles from the tumor cell surfaces. This process, when occurring at physiologic temperature (37 °C), mimics the morphological and membrane permeability changes occurring during T-lymphocyte mediated cytolysis of tumor cells. The latter is an oxygen dependent event, but it is not known whether this requirement is at the effector T cell or at the tumor cell level. The present study investigated the oxygen consumption rates of mastocytoma P815 cells induced to shed membrane vesicles by a temperature shift (0 °C/1–2 hrs → ≥20 °C). Results showed that cells undergoing the membrane vesicle shedding process had significantly higher oxygen requirements than control non-shedding cells. Inhibition of the shedding process with deuterium oxide and hexylene glycol, reduced the oxygen consumption rates of low temperature treated cells to the level of control cells. The oxygen consumption rates of the latter were unaffected by these microtubule stabilizing agents. These data indicate that the oxygen required for immune T-cell mediated lysis of tumor cells may be at the target tumor cell level.