Cytotoxicity of lymphokine-activated killer cells against human neuroblastoma cells: modulation by neuroblast differentiation.
The cytolytic activity of lymphokine-activated killer (LAK) cells against human neuroblastoma (NB) cells was investigated using the continuous NB cell lines, IMR-32, Kelly, and two subclones of SK-N-SH, SH-SY5Y (neuroblastic phenotype), and SH-EP (non-neuronal phenotype). NB cells were found to be sensitive targets of LAK. Of the SK-N-SH subclones, the neuroblasts, SH-SY5Y, were more susceptible to LAK killing than were the non-neuronal cells, SH-EP. Pretreatment of the targets SH-SY5Y and SH-EP with the differentiating agents, retinoic acid (RA, 10 microM), herbimycin A (236 nM), or nerve growth factor (10 ng/ml), did not substantially alter LAK killing. Furthermore, these differentiating agents did not measurably affect LAK activity during the cytolysis assay or with 1-h preincubation of the LAK effectors. However, co-incubation of the LAK cultures over the 3-day activation period with RA (1 microM) or PGE2 (1 microM) inhibited cytolysis by 80%, suggesting that these agents interfere with an early activation step of LAK. These results support the potential use of LAK treatment for neuroblastoma, in combination with differentiation agents that do not affect neuroblastoma sensitivities toward LAK cells. However, some differentiation agents, (e.g., RA) and endogenous prostaglandins (e.g., PGE2) may interfere with LAK activation.
Duan
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DS
Department of Pharmacy and Pharmaceutical Chemistry, School of Pharmacy, University of California, San Francisco 94143.
Farmer
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D
Rayner
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Sadee
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W
D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D003602:Cytotoxicity, Immunologic; D015232:Dinoprostone / Q000494:pharmacology; D006801:Humans; D015979:Killer Cells, Lymphokine-Activated / Q000187:drug effects / Q000502:physiology*; D009447:Neuroblastoma / Q000473:pathology / Q000628:therapy*; D018377:Neurotransmitter Agents / Q000494:pharmacology; D010641:Phenotype; D014212:Tretinoin / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D018377:Neurotransmitter Agents; D014212:Tretinoin; D015232:Dinoprostone