Okamoto M, Lee C, Oyasu R
Department of Pathology, Northwestern University Medical School, Chicago, Illinois 60611-3008, USA.
Cancer Res. 1997 Jan 1;57(1):141-6.
Interleukin (IL)-6 plays a significant role in genitourinary carcinomas. The present study was conducted to define the role of IL-6 in the growth of prostatic carcinoma and benign prostatic hyperplasia (BPH). An in vitro experiment was carried out using human prostatic carcinoma cell lines (LNCaP, which is androgen sensitive and slow growing, and DU145 and PC3, which are androgen insensitive and fast growing), and primary human epithelial and stromal cells derived from BPH. Cells were treated with recombinant human IL-6 or conditioned medium (CM) derived from the above cultured cells to identify possible paracrine and autocrine pathways. LNCaP was clearly responsive to exogenous IL-6 and to the CM derived from stromal cells, but not to the CM from LNCaP cells (P < 0.001). DU145 and PC3 were slightly stimulated to grow by exogenous IL-6 and the CM derived from both stromal and respective homologous cells (P < 0.01). In contrast, BPH-derived epithelial cells showed little or no response to IL-6. The stimulatory effect of CM on prostatic carcinoma cells was significantly reduced by the addition of anti-IL-6 antibody to the culture medium. Furthermore, the growth of DU145 and PC3 in serum-free medium was also inhibited by anti-IL-6 antibody (P < 0.001). All cell lines tested, except for LNCaP, secreted IL-6 into the culture medium. Results of reverse transcriptase-PCR analysis indicated that IL-6 receptor mRNA was present in all carcinoma cell lines but not in epithelial cells or stromal cells derived from BPH. These results suggest that IL-6 functions as a paracrine growth factor for LNCaP and as an autocrine growth factor for DU145 and PC3, but it has no stimulatory effect on epithelial cells derived from BPH.
白细胞介素（IL）-6在泌尿生殖系统癌中发挥着重要作用。本研究旨在明确IL-6在前列腺癌和良性前列腺增生（BPH）生长中的作用。采用人前列腺癌细胞系（对雄激素敏感且生长缓慢的LNCaP，以及对雄激素不敏感且生长迅速的DU145和PC3）和源自BPH的原代人上皮细胞及基质细胞进行体外实验。用重组人IL-6或上述培养细胞产生的条件培养基（CM）处理细胞，以确定可能的旁分泌和自分泌途径。LNCaP对外源性IL-6和基质细胞产生的CM有明显反应，但对LNCaP细胞产生的CM无反应（P<0.001）。外源性IL-6以及基质细胞和各自同源细胞产生的CM对DU145和PC3的生长有轻微刺激作用（P<0.01）。相比之下，源自BPH的上皮细胞对IL-6几乎没有反应。向培养基中添加抗IL-6抗体可显著降低CM对前列腺癌细胞的刺激作用。此外，抗IL-6抗体也抑制了DU145和PC3在无血清培养基中的生长（P<0.001）。除LNCaP外，所有测试的细胞系均向培养基中分泌IL-6。逆转录聚合酶链反应（RT-PCR）分析结果表明，IL-6受体mRNA存在于所有癌细胞系中，但不存在于源自BPH的上皮细胞或基质细胞中。这些结果表明，IL-6作为LNCaP的旁分泌生长因子以及DU145和PC3的自分泌生长因子发挥作用，但对源自BPH的上皮细胞没有刺激作用。
