Department of Histology and Embryology, Department of Human Morphology and Embryology, Wroclaw Medical University, Chałubińskiego 6a St, 50-368 Wrocław, Poland.
Department of Physiotherapy, Wroclaw University School of Physical Education, Ignacego Jana Paderewskiego 35 Av., 51-612 Wroclaw, Poland.
Int J Mol Sci. 2020 Oct 26;21(21):7955. doi: 10.3390/ijms21217955.
A neoplastic tumor consists of cancer cells that interact with each other and non-cancerous cells that support the development of the cancer. One such cell are tumor-associated macrophages (TAMs). These cells secrete many chemokines into the tumor microenvironment, including especially a large amount of CCL18. This chemokine is a marker of the M2 macrophage subset; this is the reason why an increase in the production of CCL18 is associated with the immunosuppressive nature of the tumor microenvironment and an important element of cancer immune evasion. Consequently, elevated levels of CCL18 in the serum and the tumor are connected with a worse prognosis for the patient. This paper shows the importance of CCL18 in neoplastic processes. It includes a description of the signal transduction from PITPNM3 in CCL18-dependent migration, invasion, and epithelial-to-mesenchymal transition (EMT) cancer cells. The importance of CCL18 in angiogenesis has also been described. The paper also describes the effect of CCL18 on the recruitment to the cancer niche and the functioning of cells such as TAMs, regulatory T cells (T), cancer-associated fibroblasts (CAFs) and tumor-associated dendritic cells (TADCs). The last part of the paper describes the possibility of using CCL18 as a therapeutic target during anti-cancer therapy.
肿瘤由相互作用的癌细胞和支持癌症发展的非癌细胞组成。其中一种细胞是肿瘤相关巨噬细胞（TAMs）。这些细胞向肿瘤微环境中分泌许多趋化因子，包括大量的 CCL18。这种趋化因子是 M2 巨噬细胞亚群的标志物；这就是为什么 CCL18 产量的增加与肿瘤微环境的免疫抑制性质以及癌症免疫逃逸的一个重要因素有关。因此，血清和肿瘤中 CCL18 水平的升高与患者预后不良有关。本文展示了 CCL18 在肿瘤发生过程中的重要性。它包括描述了 PITPNM3 在 CCL18 依赖性迁移、侵袭和上皮间质转化（EMT）癌细胞中的信号转导。还描述了 CCL18 在血管生成中的重要性。本文还描述了 CCL18 对癌症生态位招募和 TAMs、调节性 T 细胞（T）、癌症相关成纤维细胞（CAFs）和肿瘤相关树突状细胞（TADCs）等细胞功能的影响。本文的最后一部分描述了在抗癌治疗期间使用 CCL18 作为治疗靶点的可能性。
