INTERLEUKIN-6 AND RENAL-CELL CANCER - PRODUCTION, REGULATION, AND GROWTH EFFECTS
INTERLEUKIN-6 AND RENAL-CELL CANCER - PRODUCTION, REGULATION, AND GROWTH EFFECTS
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DOI：
10.1007/bf01741856
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发表时间：
1992-06-01
影响因子：
5.8
通讯作者：
BELLDEGRUN, A
中科院分区：
文献类型：
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作者：
KOO, AS;ARMSTRONG, C;BELLDEGRUN, A
白细胞介素 6 (IL-6) 是一种最近被鉴定具有抗肿瘤活性的多效细胞因子。我们研究了肾细胞癌 (RCC) 产生 IL-6 以及 IL-6 对 RCC 生长的影响。使用免疫过氧化物酶染色，在四种肾肿瘤系中的四种以及新鲜肾切除肾细胞癌的肿瘤细胞中检测到细胞质 IL-6。我们发现，在测试的 10 个 RCC 肿瘤系中，有 7 个在基础培养条件下表达了 IL-6 mRNA。通过 B9 测定测量，所有 10 个 RCC 肿瘤系均产生生物活性 IL-6。添加肿瘤坏死因子-α (TNF-α) 显着增强了 5 个 RCC 肿瘤系中 IL-6 mRNA 的表达（P < 0.05）。干扰素γ-IFN-γ和TNF-α的组合进一步增强了单独使用TNF-α时观察到的增加的IL-6 mRNA积累(P < 0.05)。 TNF-α 还显着刺激具有生物活性的 IL-6 的产生（P < 0.01）。此外，发现 IFN-γ 和 TNF-α 可以协同增强 IL-6 的生物活性（P < 0.05）。还在两个实验系统中研究了 IL-6 对 RCC 的生长影响：通过胸苷摄取测定，发现 IL-6 在 6 个 RCC 肿瘤系中的 6 个中刺激增殖反应；然而，六种肿瘤系中只有一种的增殖反应增加超过 21% (113%)。在克隆形成实验中进一步测试了 IL-6 的生长效果。其中一种测试的肿瘤细胞系显示出高达 200% 的增强生长反应。我们的结论是IL-6是由RCC产生的； TNF-α 可以增强这种产生，并在 mRNA 和蛋白质水平上与 IFN-γ 产生协同效应。反过来，IL-6 可能对某些 RCC 肿瘤系具有适度的刺激生长作用。
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-alpha (TNF-alpha) significantly augmented the expression of IL-6 mRNA in five RCC tumor lines (P < 0.05). The combination of interferon gamma-IFN-gamma and TNF-alpha further enhanced the augmented IL-6 mRNA accumulation seen with TNF-alpha alone (P < 0.05). TNF-alpha also significantly stimulated the production of biologically active IL-6 (P < 0.01). Furthermore, IFN-gamma and TNF-alpha 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 TNF-alpha with synergistic effects seen with IFN-gamma at both mRNA and protein levels. In turn, IL-6 may have a modest stimulatory growth effect on certain RCC tumor lines.