GENERATION OF A SMALL-CELL LUNG-CANCER VARIANT RESISTANT TO LYMPHOKINE-ACTIVATED KILLER (LAK) CELLS - ASSOCIATION WITH RESISTANCE TO A LAK CELL-DERIVED, CYTOSTATIC FACTOR

Cells of OS2-RA, a human small cell lung cancer line sensitive to lymphokine-activated killer (LAK) cells, were repeatedly cocultured with human LAK cells. Fourteen cycles of the coculture produced a variant, termed OS2-RA-R, capable of growing successfully in the presence of LAK cells. OS2-RA-R sho...

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Published in:Cancer research (Chicago, Ill.) Ill.), 1992-06, Vol.52 (12), p.3310-3316
Main Authors: TACHIBANA, WATANABE, M, TANIO, Y, HAYASHI, S, HOSOE, S, SAITO, S, MATSUNASHI, M, OSAKI, T, SHIGEDO, Y, MASUNO, T, KAWASE
Format: Article
Language:English
Subjects:
Animals
Antineoplastic agents
Autacoids - isolation & purification
Autacoids - metabolism
Biological and medical sciences
Carcinoma, Small Cell - pathology
Cytokines - isolation & purification
Cytokines - metabolism
Drug Resistance
Humans
Immunotherapy
Interferon-gamma - pharmacology
Killer Cells, Lymphokine-Activated - metabolism
Life Sciences & Biomedicine
Lung Neoplasms - pathology
Medical sciences
Mice
Mice, Inbred BALB C
Mice, Nude
Oncology
Pharmacology. Drug treatments
Science & Technology
Tumor Cells, Cultured
Tumor Necrosis Factor-alpha - pharmacology
Tumor Stem Cell Assay
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Summary:Cells of OS2-RA, a human small cell lung cancer line sensitive to lymphokine-activated killer (LAK) cells, were repeatedly cocultured with human LAK cells. Fourteen cycles of the coculture produced a variant, termed OS2-RA-R, capable of growing successfully in the presence of LAK cells. OS2-RA-R showed a moderate resistance to lysis by LAK cells in 4-h Cr-51 release assays. OS2-RA-R acted positively as a cold target for lysis of OS2-RA by LAK cells, suggesting no loss of the binding site for LAK cells on the cell surface of the variant. On the other hand, LAK cells were shown to produce a factor capable of suppressing the proliferation of OS2-RA and certain other cell lines but not lymphocytes. Interestingly, OS2-RA-R exhibited a substantial resistance to the cytostatic activity of LAK cell supernatants. The cytostatic factor, eluted at the 57-kDa fraction in gel filtration, showed no activity of interleukin 1, gamma-interferon, transforming growth factor-beta, or tumor necrosis factor. These results suggest that LAK cells exhibit antitumor activity through not only rapid cytolysis but also slow-acting cytokine production, and the successful growth of OS2-RA-R in a coculture with LAK cells is the result of acquiring resistance to these two different LAK cell phenomena.
ISSN:0008-5472
1538-7445