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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.

Abstract
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.
AuthorsI Tachibana, M Watanabe, Y Tanio, S Hayashi, S Hosoe, S Saito, M Matsunashi, T Osaki, Y Shigedo, T Masuno
JournalCancer research (Cancer Res) Vol. 52 Issue 12 Pg. 3310-6 (Jun 15 1992) ISSN: 0008-5472 [Print] United States
PMID1350752 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Autacoids
  • Cytokines
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma
Topics
  • Animals
  • Autacoids (isolation & purification, metabolism)
  • Carcinoma, Small Cell (pathology)
  • Cytokines (isolation & purification, metabolism)
  • Drug Resistance
  • Humans
  • Interferon-gamma (pharmacology)
  • Killer Cells, Lymphokine-Activated (metabolism)
  • Lung Neoplasms (pathology)
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Tumor Cells, Cultured
  • Tumor Necrosis Factor-alpha (pharmacology)
  • Tumor Stem Cell Assay

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