Interleukin-6 as a paracrine and autocrine growth factor in human prostatic carcinoma cells in vitro.
Interleukin-6 as a paracrine and autocrine growth factor in human prostatic carcinoma cells in vitro.
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发表时间：
1997
期刊：
影响因子：
11.2
通讯作者：
Masato Okamoto;Chung Lee;Ryoichi Oyasu
中科院分区：
文献类型：
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作者：
Masato Okamoto;Chung Lee;Ryoichi Oyasu
白细胞介素 (IL)-6 在泌尿生殖癌中发挥重要作用。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。使用人前列腺癌细胞系（雄激素敏感且生长缓慢的LNCaP，以及雄激素不敏感且生长快速的DU145和PC3）以及源自BPH的原代人上皮细胞和基质细胞进行体外实验。用重组人 IL-6 或源自上述培养细胞的条件培养基 (CM) 处理细胞，以鉴定可能的旁分泌和自分泌途径。 LNCaP 对外源性 IL-6 和源自基质细胞的 CM 明显有反应，但对来自 LNCaP 细胞的 CM 没有反应（P < 0.001）。 DU145 和 PC3 被外源性 IL-6 和源自基质细胞和各自同源细胞的 CM 轻微刺激生长（P < 0.01）。相反，BPH 衍生的上皮细胞对 IL-6 几乎没有反应或没有反应。通过向培养基中添加抗IL-6抗体，CM对前列腺癌细胞的刺激作用显着降低。此外，DU145和PC3在无血清培养基中的生长也被抗IL-6抗体抑制(P < 0.001)。除 LNCaP 外，所有测试的细胞系均将 IL-6 分泌到培养基中。逆转录酶-PCR分析结果表明IL-6受体mRNA存在于所有癌细胞系中，但不存在于来自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作为DU145和PC3的自分泌生长因子发挥作用，但其对源自BPH的上皮细胞没有刺激作用。
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.