Department of Pathology, School of Basic Medical Sciences, Anhui Medical University, Hefei, 230032, Anhui, China.
Department of Hematology, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, Anhui, China.
Lab Invest. 2022 Dec;102(12):1377-1388. doi: 10.1038/s41374-022-00824-5. Epub 2022 Jul 18.
In recent years, CC chemokine receptor 2 (CCR2) has been found to be involved in tumor growth, angiogenesis, epithelial mesenchymal transition, metastasis, and immune escape. CCR2 overexpression was first identified as a poor prognostic predictor in diffuse large B-cell lymphoma (DLBCL) in our published article, but the mechanisms involved remain unknown. In this work, we collected data from another 138 patients with DLBCL data and verified the CCR2 expression level and its relationship to clinicopathological characteristics. Furthermore, we explored the possible mechanisms via in vitro and in vivo experiments. We showed that CCR2 overexpression was an independent prognostic marker and predicted shorter overall survival (OS) and progression-free survival (PFS) in patients with DLBCL. Blockade of CCR2 expression with a CCR2 antagonist inhibited tumor cell proliferation, migration, and anti-apoptosis ability in vitro by affecting the PI3K/Akt signaling pathway and the p38 MAPK signaling pathway. Furthermore, administration of a CCR2 antagonist decreased tumor growth and dissemination of DLBCL cells and increased survival time in the xenograft model. Our study demonstrates that CCR2 expression plays an important role in the development of DLBCL by stimulating cell proliferation, migration, and anti-apoptosis. Therefore, the inhibition of CCR2 may be a potential target for anticancer therapy in DLBCL.
近年来，CC 趋化因子受体 2（CCR2）被发现参与肿瘤生长、血管生成、上皮间质转化、转移和免疫逃逸。在我们发表的文章中首次发现 CCR2 过表达是弥漫性大 B 细胞淋巴瘤（DLBCL）不良预后的预测指标，但具体机制尚不清楚。在这项工作中，我们收集了另外 138 例 DLBCL 患者的数据，验证了 CCR2 的表达水平及其与临床病理特征的关系。此外，我们还通过体外和体内实验探讨了可能的机制。我们表明，CCR2 过表达是独立的预后标志物，可预测 DLBCL 患者总生存期（OS）和无进展生存期（PFS）更短。用 CCR2 拮抗剂阻断 CCR2 表达可通过影响 PI3K/Akt 信号通路和 p38 MAPK 信号通路，抑制肿瘤细胞增殖、迁移和抗凋亡能力。此外，CCR2 拮抗剂的给药可减少 DLBCL 细胞的肿瘤生长和扩散，并增加异种移植模型中的存活时间。我们的研究表明，CCR2 表达通过刺激细胞增殖、迁移和抗凋亡，在 DLBCL 的发展中起重要作用。因此，抑制 CCR2 可能是 DLBCL 抗癌治疗的一个潜在靶点。
