Characterization of an oxidation-resistant tumor cell line and its sensitivity to immune response and chemotherapy

Abstract

Aerobic cells have several scavenger systems for protection from reactive oxygen species (ROS). We developed an ROS-resistant variant of the human erythroleukemic cell line K562 by culturing cells in glucose oxidase to produce hydrogen peroxide. Testing the activity of the scavenger systems for ROS showed these cells had a 25- to 28-fold increase in catalase activity. We therefore termed this variant cell line K562-CAT. There was no similar increase in glutathione content or activity of superoxide dismutase and glutathione peroxidase. To determine what effect the increased catalase activity would have on the immune response to these tumor cells, we compared K562 and K562-CAT sensitivity to tumor necrosis factor-alpha (TNF alpha) activated polymorphonuclear neutrophil (PMN), natural killer (NK), and lymphokine-activated killer (LAK) cells. K562-CAT showed a significant increase in resistance to TNF alpha-activated PMN but not to NK or LAK, confirming the role of ROS in the former but not the latter. We also tested K562-CAT sensitivity to cisplatin and mitomycin C, agents known to involve ROS in their cytotoxic mechanism. There was no increased resistance in K562-CAT compared to parental K562, indicating that catalase is not involved in tumor cell resistance to those drugs. Given the characteristics of its resistance to the immune response, K562-CAT or a similar catalase-hyperexpressing cell line could be useful in determining the significance of TNF alpha-activated PMN in antitumor defenses.