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 showed a moderate resistance to lysis by LAK cells in 4-h 51Cr 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.
Department of Internal Medicine III, Osaka University Medical School, Japan.
I
I
Tachibana
M
M
Watanabe
Y
Y
Tanio
S
S
Hayashi
S
S
Hosoe
S
S
Saito
M
M
Matsunashi
T
T
Osaki
Y
Y
Shigedo
T
T
Masuno
D000818:Animals; D012898:Autacoids / Q000302:isolation & purification / Q000378:metabolism*; D018288:Carcinoma, Small Cell / Q000473:pathology*; D016207:Cytokines / Q000302:isolation & purification / Q000378:metabolism*; D004351:Drug Resistance; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D015979:Killer Cells, Lymphokine-Activated / Q000378:metabolism*; D008175:Lung Neoplasms / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014410:Tumor Stem Cell Assay
D012898:Autacoids; D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma