The presentation and regulation of the IL-8 network in the epithelial cancer stem-like cell niche in patients with colorectal cancer
The presentation and regulation of the IL-8 network in the epithelial cancer stem-like cell niche in patients with colorectal cancer
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DOI：
10.1016/j.biopha.2022.113252
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发表时间：
2022-06-07
影响因子：
7.5
通讯作者：
Goll, Rasmus
中科院分区：
文献类型：
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作者：
Cui, Guanglin;Li, Gui;Goll, Rasmus
背景资料：越来越多的证据表明，肿瘤干细胞（cancer stem-like cells，CSCs）的生物学行为受其周围生态位的调控，其中细胞因子是CSCs与其微环境相互作用的主要介质之一。研究方法：我们使用定量实时PCR（q-PCR）、免疫组织化学（IHC）和双重免疫荧光技术表征了腺瘤/CRC上皮中CSC和白细胞介素（IL）-8网络的表达。此外，在体外检查IL-1 β刺激结肠癌Caco-2细胞中上皮IL-8产生的能力，并通过酶联免疫吸附测定（ELISA）测量IL-8产物。结果如下：IHC观察显示腺瘤和CRC上皮中CSC和IL-8的表达增加，q-PCR结果显示腺瘤和CRC组织中IL-1 β转录物的表达增加与IL-8转录物水平增加密切相关。双重免疫荧光图像显示，在CRC组织切片中，IL-8受体IL-8 RA和IL-8 RB与LGR 5标记的CSC共表达。体外实验结果表明，Caco-2细胞与浓度为1、5、10和20 ng/ml的IL-1 β共培养时，IL-8的释放呈剂量依赖性，而IL-1 β受体拮抗剂可特异性抑制IL-8的释放。结论：这些结果表明，从癌前腺瘤阶段到CRC阶段，CSC的小生境中IL-8网络的活化，其可能受到CRC细胞中IL-1 β的刺激。
Background: Accumulative evidence suggests that the biological behavior of cancer stem-like cells (CSCs) is regulated by their surrounding niche, in which cytokines function as one of the main mediators for the interaction between CSCs and their microenvironment in the colorectal cancer (CRC). Methods: We characterized the presentation of CSCs and the interleukin (IL)-8 network in the adenoma/CRC epithelium using quantitative real-time PCR (q-PCR), immunohistochemistry (IHC) and double immunofluorescence. In addition, the capacity of IL-1 beta to stimulate epithelial IL-8 production in colon cancer Caco-2 cells was examined in vitro and the IL-8 product was measured by enzyme-linked immunosorbent assay (ELISA). Results: IHC observation showed increased expression of both CSCs and IL-8 in the adenoma and CRC epithelium, and q-PCR results revealed that increased expression of IL-1 beta transcript was strongly correlated with increased IL-8 transcript levels in both adenoma and CRC tissues. Double immunofluorescence images demonstrated the coexpression of the IL-8 receptors IL-8RA and IL-8RB with LGR5 labeled CSCs in CRC tissue sections. Consistently, in vitro experiments showed that coculture of Caco-2 cells with IL-1 beta at concentrations of 1, 5, 10 and 20 ng/ml resulted in a dose-dependent release of IL-8, which could be specifically inhibited by cotreatment with the IL-1 beta receptor antagonist. Conclusions: These results demonstrate activation of the IL-8 network in the niche of CSCs from the precancerous adenoma stage to the CRC stage, which is potentially stimulated by IL-1 beta in CRC cells.