Human neutrophil-mediated lysis of ovarian cancer cells.
Because of recent questions concerning the sensitivity of human tumor cells to neutrophil-induced oxidative injury, we studied six freshly obtained human ovarian cancer (OC) specimens. Stimulation of neutrophils (PMNs) by phorbol myristate acetate (PMA) did not result in OC cytolysis during the first nine hours of incubation. However, three of six specimens were significantly lysed by stimulated PMNs when assay length was increased to 18 hours. Cytotoxicity was mediated by PMN production of reactive oxidative intermediates (ROIs). Presentation of ROIs to OC targets as preformed or enzymatically generated molecules in cell-free systems duplicated the enhanced lysis at 18 hours (as compared with six hours). Since addition of catalase at three or six hours did not inhibit enhanced lysis at 18 hours (achieved by PMNs or in cell-free systems), it appears that an initial ROI-mediated lethal event occurs early, but longer incubations are required for the event to become manifested as cell death. These data suggest that shorter assays may underestimate the potential of PMNs as effector cells against human tumor cells.
Lichtenstein
A
A
Division of Hematology/Oncology, VA Wadsworth Medical Center, Los Angeles, CA 90073.
Seelig
M
M
Berek
J
J
Zighelboim
J
J
D000230:Adenocarcinoma / Q000276:immunology* / Q000378:metabolism; D002474:Cell-Free System; D003602:Cytotoxicity, Immunologic; D005260:Female; D005609:Free Radicals; D006105:Granulomatous Disease, Chronic / Q000276:immunology; D006801:Humans; D006878:Hydroxides / Q000633:toxicity; D017665:Hydroxyl Radical; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000276:immunology* / Q000378:metabolism; D010100:Oxygen / Q000633:toxicity
D005609:Free Radicals; D006878:Hydroxides; D017665:Hydroxyl Radical; D010100:Oxygen