Division of Cancer Biology, CSIR-Central Drug Research Institute (CDRI), Lucknow 226031, India.
Division of Cancer Biology, CSIR-Central Drug Research Institute (CDRI), Lucknow 226031, India.
Cytokine. 2022 Aug;156:155916. doi: 10.1016/j.cyto.2022.155916. Epub 2022 May 26.
A subpopulation of cells in many cancers has stem cell traits, mediates metastasis, and contributes to treatment resistance. These cells are considered as cancer stem cells (CSCs). CSC properties of tumor cells are immensely regulated by close interactions with tumor microenvironment components such as mesenchymal stem cells, tumor related fibroblasts, adipocytes, endothelial cells, and immune cells via the intricate network of cytokines, chemokines, and growth factors. Inflammatory cytokines including interleukin (IL)-1, IL-6, and IL-8 play a major role in these interactions via the activation of signal transduction pathways like Stat3/NF-κB etc. in stromal and tumor cells. The activation of these pathways increases the release of more cytokines, resulting in positive feedback loops which help in CSC self-renewal. The pathways controlled by these cytokine loops are similar to those that are active during chronic inflammation and wound healing, suggesting that they might have critical role in establishing relationship between inflammation and cancer. Anti-inflammatory drugs have been identified to inhibit these cytokines and their receptor mediated pathways. These agents have the potential to target CSCs by inhibiting signals from the tumor microenvironment and considered to be a potential candidate for future therapeutics. The significance of cytokines released from the tumor microenvironment in different phases of cancer, as well as their potential application in cancer therapeutics is discussed in this article.
许多癌症中的细胞亚群具有干细胞特征，介导转移，并导致治疗耐药。这些细胞被认为是癌症干细胞 (CSC)。肿瘤细胞的 CSC 特性受到与肿瘤微环境成分（如间充质干细胞、肿瘤相关成纤维细胞、脂肪细胞、内皮细胞和免疫细胞）的密切相互作用的极大调节，通过细胞因子、趋化因子和生长因子的复杂网络进行调节。包括白细胞介素 (IL)-1、IL-6 和 IL-8 在内的炎症细胞因子通过激活信号转导途径（如 Stat3/NF-κB 等）在基质和肿瘤细胞中发挥主要作用。这些途径的激活增加了更多细胞因子的释放，导致正反馈循环，有助于 CSC 的自我更新。这些细胞因子循环控制的途径与慢性炎症和伤口愈合过程中活跃的途径相似，表明它们可能在炎症和癌症之间的关系建立中起关键作用。已经发现抗炎药物可以抑制这些细胞因子及其受体介导的途径。这些药物通过抑制肿瘤微环境中的信号来靶向 CSC，并被认为是未来治疗的潜在候选药物。本文讨论了肿瘤微环境中释放的细胞因子在癌症不同阶段的重要性，以及它们在癌症治疗中的潜在应用。
