Overexpression of interleukin-6 in human basal cell carcinoma cell lines increases anti-apoptotic activity and tumorigenic potency
Overexpression of interleukin-6 in human basal cell carcinoma cell lines increases anti-apoptotic activity and tumorigenic potency
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DOI：
10.1038/sj.onc.1204076
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发表时间：
2001-01-11
期刊：
影响因子：
8
通讯作者：
Kuo, ML
中科院分区：
文献类型：
--
作者：
Jee, SH;Shen, SC;Kuo, ML
白细胞介素-6 (IL-6) 是一种多效性细胞因子，能够调节细胞的多种功能，例如急性期反应和炎症。 IL-6 产生过多或不足可能会导致某些皮肤疾病。本研究的目的是探讨IL-6在基底细胞癌（BCC）肿瘤发生中的可能作用，首先，ffe将CMV启动子控制下的IL-6表达载体转染人BCC细胞，并成功获得IL-6过表达克隆（BCC/IL-6-c1和BCC/IL-6-c2）和混合物（BCC/IL-6）。使用 H-3-胸苷脉冲掺入测定的 DNA 合成测定表明，表达 IL-6 的 BCC 细胞表现出比新对照或亲本 BCC 细胞高得多的 DNA 合成率。 Ne 还检测到在软琼脂中形成的表达 IL-6 的细胞集落比在载体对照细胞中更丰富。此外，BCC/IL-6 细胞（而非载体对照细胞）对紫外线和光动力疗法 (PDT) 诱导的细胞凋亡具有抵抗力，正如使用 DNA 碎片和形态变化分析所证实的那样。免疫印迹分析显示，抗凋亡蛋白Mcl-1在IL-6转染子中特异性上调，但在对照细胞中没有上调，反义mcl-1瞬时转染IL-6转染子，经UV处理大大提高了其凋亡频率。在肿瘤发生实验中，IL-6转染克隆在裸鼠中形成肿瘤的速度比对照细胞更快。通过病理检查，这些肿瘤似乎高度血管化。ffe 发现 IL-6 转染的细胞表达两种血管生成因子（环化酶 (Cos)-2 和血管内皮生长因子 (VEGF)）水平升高，这支持了这一发现。这些结果表明IL-6的过度表达通过抑制细胞凋亡和积极促进血管生成来增强BCC细胞的致瘤活性。
Interleukin-6 (IL-6) is a pleiotropic cytokine that is capable of modulating the diverse functions of cells such as acute phase responses and inflammation. Excessive or insufficient production of IL-6 may contribute to certain diseases of the skin. The aim of this study was to investigate the possible role of IL-6 in the tumorigenesis of basal cell carcinoma (BCC), Initially, ffe transfected IL-6 expression vector, under the control of a CMV promoter, into human BCC cells and successfully obtained IL-6-overespressing clones (BCC/IL-6-c1 and BCC/IL-6-c2) and a mixture (BCC/IL-6). DNA synthesis assay determined using H-3-thymidine pulse incorporation revealed that IL-6-expressing BCC cells exhibited a much higher DNA synthesis rate than the neo control or parental BCC cells. Ne also detected a greater abundance of IL-6-expressing cell colonies formed in soft agar than in the vector control cells. Furthermore, BCC/IL-6 cells, but not vector control cells, were resistant to UV and photodynamic therapy (PDT)-induced apoptosis, as confirmed using DNA fragmentation and morphologic change analyses. Immunoblot analysis showed that Mcl-1, an anti-apoptotic protein, was specifically up-regulated IL-6 transfectants but not in the control cells, Transient transfection of IL-6 transfectants with antisense mcl-1 greatly enhanced their apoptosis frequency by UV treatment, In tumorigenesis assay, IL-6 transfected clones formed tumors in nude mice more rapidly than the control cells. These tumors appeared to be highly vascularized using pathological examination, Supportive of this finding, ffe found that IL-6 transfected cells expressed elevated levels of two angiogenic factors, cycloosygenase (Cos)-2 and vascular endothelial growth factor (VEGF). These results suggest that overexpression of IL-6 enhances the tumorigenic activity of BCC cells by both suppressing apoptosis and actively promoting angiogenesis.