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Interleukin-6 and renal cell cancer: Production, regulation, and growth effects

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Summary

Interleukin-6 (IL-6) is a recently characterized pleiotropic cytokine with antitumor activity. We investigated the production of IL-6 by renal cell cancer (RCC) and the growth effects of IL-6 on RCC. Using immunoperoxidase staining, cytoplasmic IL-6 was detected in four of four renal tumor lines and in tumor cells from freshly nephrectomized RCC. We found that IL-6 mRNA was expressed at basal culture conditions by seven of ten RCC tumor lines tested. Biologically active IL-6, as measured by the B9 assay, was produced by all ten RCC tumor lines. The addition of tumor necrosis factor α (TNFα) significantly augmented the expression of IL-6 mRNA in five RCC tumor lines (P <0.05). The combination of interferon γ IFNγ and TNFα further enhanced the augmented IL-6 mRNA accumulation seen with TNFα alone (P <0.05). TNFα also significantly stimulated the production of biologically active IL-6 (P <0.01). Furthermore, IFNγ and TNFα were found to enhance IL-6 bioactivity synergistically (P <0.05). The growth effects of IL-6 on RCC were also investigated in two experimental systems: IL-6 was found to stimulate proliferative responses in six of six RCC tumor lines as measured by thymidine-uptake assays; however, only one of six tumor lines displayed an increase in proliferative response of greater than 21% (113%). The growth effect of IL-6 was further tested in clonogenic assays. One of the tumor lines tested displayed an enhanced growth response of up to 200%. We conclude that IL-6 is produced by RCC; this production is enhanced by TNFα with synergistic effects seen with IFNγ at both mRNA and protein levels. In turn, IL-6 may have a modest stimulatory growth effect on certain RCC tumor lines.

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Authors and Affiliations

  1. Immunotherapy Laboratory, Division of Urology, Department of Surgery, and the Jonsson Comprehensive Cancer Center, UCLA School of Medicine, Los Angeles, California, USA

    Alec S. Koo, Cathy Armstrong, Bernard Bochner, Tomoyuki Shimabukuro, Cho-Lea Tso, Jean B. deKernion & Arie Belldegrun

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  1. Alec S. Koo
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  2. Cathy Armstrong
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  3. Bernard Bochner
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  4. Tomoyuki Shimabukuro
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  5. Cho-Lea Tso
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  6. Jean B. deKernion
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This work was supported in part by National Institutes of Health Grant CA 522 499-01, and the Margaret Early Foundation

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Koo, A.S., Armstrong, C., Bochner, B. et al. Interleukin-6 and renal cell cancer: Production, regulation, and growth effects. Cancer Immunol Immunother 35, 97–105 (1992). https://doi.org/10.1007/BF01741856

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