Immunology Research Center, National Health Research Institutes, Miaoli 35053, Taiwan.
Institute of Molecular and Genomic Medicine, National Health Research Institutes, Miaoli 35053, Taiwan.
J Immunol Res. 2016;2016:4368101. doi: 10.1155/2016/4368101. Epub 2016 Dec 27.
Cancer stem cells (CSCs) are a small population of cancer cells that exhibit stemness. These cells contribute to cancer metastasis, treatment resistance, and relapse following therapy; therefore, they may cause malignancy and reduce the success of cancer treatment. Nuclear factor kappa B- (NF-B-) mediated inflammatory responses increase stemness in cancer cells, and CSCs constitutively exhibit higher NF-B activation, which in turn increases their stemness. These opposite effects form a positive feedback loop that further amplifies inflammation and stemness in cancer cells, thereby expanding CSC populations in the tumor. Toll-like receptors (TLRs) activate NF-B-mediated inflammatory responses when stimulated by carcinogenic microbes and endogenous molecules released from cells killed during cancer treatment. NF-B activation by extrinsic TLR ligands increases stemness in cancer cells. Moreover, it was recently shown that increased NF-B activity and inflammatory responses in CSCs may be caused by altered TLR signaling during the enrichment of stemness in cancer cells. Thus, the activation of TLR signaling by extrinsic and intrinsic factors drives a positive interplay between inflammation and stemness in cancer cells.
癌症干细胞（CSCs）是一小群具有干细胞特性的癌细胞。这些细胞有助于癌症转移、治疗耐药和治疗后复发；因此，它们可能导致恶性肿瘤并降低癌症治疗的成功率。核因子 kappa B-（NF-B-）介导的炎症反应增加了癌细胞的干细胞特性，而 CSCs 持续表现出更高的 NF-B 激活，这反过来又增加了它们的干细胞特性。这些相反的效应形成了一个正反馈环，进一步放大了癌细胞中的炎症和干细胞特性，从而扩大了肿瘤中的 CSC 群体。Toll 样受体（TLRs）在受到致癌微生物和癌症治疗过程中杀死的细胞释放的内源性分子刺激时，激活 NF-B 介导的炎症反应。外在 TLR 配体对 NF-B 的激活增加了癌细胞的干细胞特性。此外，最近的研究表明，CSC 中 NF-B 活性和炎症反应的增加可能是由于在癌细胞中富集干细胞特性时 TLR 信号转导发生改变所致。因此，外在和内在因素对 TLR 信号的激活促使癌细胞中的炎症和干细胞特性之间产生正相互作用。
