Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050000, People's Republic of China; Neurological Laboratory of Hebei Province, Shijiazhuang, Hebei, 050000, People's Republic of China.
Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050000, People's Republic of China; Neurological Laboratory of Hebei Province, Shijiazhuang, Hebei, 050000, People's Republic of China; Institute of Cardiocerebrovascular Disease, Shijiazhuang, Hebei, 050000, People's Republic of China.
Exp Cell Res. 2021 Feb 15;399(2):112467. doi: 10.1016/j.yexcr.2020.112467. Epub 2021 Jan 8.
Tumor-associated macrophages (TAM), which are found in the tumor microenvironment of solid tumors, not only mediate cancer immune evasion but also promote tumor growth. The transcription factor NF-κB, which is a crucial link between inflammation and tumors, can accelerate tumor occurrence and development. NEMO, the regulatory subunit of the IKK complex, plays a pivotal role in activating the NF-κB signaling pathway. However, the function of myeloid NEMO in the tumor microenvironment remains unclear. Here, we found that conditional knockout of NEMO in myeloid cells promoted tumor growth in a transplanted cancer mouse model. In Nemo lyz-cre mice, the deletion of Nemo in myeloid cells increased the recruitment of M2 macrophages and myeloid-derived suppressor cells (MDSCs) into the tumor, reduced the expression of apoptosis-related proteins, and upregulated the expression of the chemokine receptor CCR2, thereby promoting tumor growth in vivo. Then, we showed that blocking the MCP1-CCR2 pathway could inhibit tumor growth, especially in mice with myeloid NEMO deletion. In this study, we examined the mechanism of NEMO in myeloid cells and explored the role of NEMO in the prevention and treatment of cancer.
肿瘤相关巨噬细胞（TAM）存在于实体瘤的肿瘤微环境中，不仅介导癌症免疫逃逸，还促进肿瘤生长。转录因子 NF-κB 是炎症与肿瘤之间的关键环节，它可以加速肿瘤的发生和发展。IKK 复合物的调节亚基 NEMO 在激活 NF-κB 信号通路中起着关键作用。然而，髓系细胞中 NEMO 的功能在肿瘤微环境中尚不清楚。在这里，我们发现髓系细胞中 NEMO 的条件性缺失促进了移植癌症小鼠模型中的肿瘤生长。在 Nemo lyz-cre 小鼠中，髓系细胞中 Nemo 的缺失增加了 M2 巨噬细胞和髓源性抑制细胞（MDSCs）向肿瘤的募集，降低了凋亡相关蛋白的表达，并上调了趋化因子受体 CCR2 的表达，从而促进了体内肿瘤的生长。然后，我们表明阻断 MCP1-CCR2 通路可以抑制肿瘤生长，特别是在髓系 NEMO 缺失的小鼠中。在这项研究中，我们研究了 NEMO 在髓系细胞中的作用机制，并探索了 NEMO 在癌症预防和治疗中的作用。
