Division of Chronic Inflammation and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Institute of Virology, Technical University of Munich, Munich, Germany.
Adv Exp Med Biol. 2021;1302:1-14. doi: 10.1007/978-3-030-62658-7_1.
The C-C motif chemokine ligand 2 (CCL2) is a crucial mediator of immune cell recruitment during microbial infections and tissue damage. CCL2 is also frequently overexpressed in cancer cells and other cells in the tumor microenvironment, and a large body of evidence indicates that high CCL2 levels are associated with more aggressive malignancies, a higher probability of metastasis, and poorer outcomes in a wide range of cancers. CCL2 plays a role in recruiting tumor-associated macrophages (TAMs), which adopt a pro-tumorigenic phenotype and support cancer cell survival, facilitate tumor cell invasion, and promote angiogenesis. CCL2 also has direct, TAM-independent effects on tumor cells and the tumor microenvironment, including recruitment of other myeloid subsets and non-myeloid cells, maintaining an immunosuppressive environment, stimulating tumor cell growth and motility, and promoting angiogenesis. CCL2 also plays important roles in the metastatic cascade, such as creating a pre-metastatic niche in distant organs and promoting tumor cell extravasation across endothelia. Due to its many roles in tumorigenesis and metastatic processes, the CCL2-CCR2 signaling axis is currently being pursued as a potential therapeutic target for cancer.
C-C 基序趋化因子配体 2（CCL2）是微生物感染和组织损伤过程中免疫细胞募集的关键介质。CCL2 也在癌细胞和肿瘤微环境中的其他细胞中经常过表达，大量证据表明高 CCL2 水平与侵袭性更强的恶性肿瘤、更高的转移概率和更差的预后相关。CCL2 在招募肿瘤相关巨噬细胞（TAMs）方面发挥作用，TAMs 采用促肿瘤发生的表型并支持癌细胞存活，促进肿瘤细胞侵袭，并促进血管生成。CCL2 还对肿瘤细胞和肿瘤微环境具有直接的、TAM 非依赖性的影响，包括招募其他髓系细胞亚群和非髓系细胞，维持免疫抑制环境，刺激肿瘤细胞生长和迁移，并促进血管生成。CCL2 在转移级联反应中也起着重要作用，例如在远处器官中创建一个预先转移的生态位，并促进肿瘤细胞穿过内皮的外渗。由于 CCL2-CCR2 信号轴在肿瘤发生和转移过程中具有许多作用，因此目前正在将其作为癌症的潜在治疗靶点进行研究。
