MIP-1 gamma/CCL9/CCL10  (趋化因子 CCL9/CCL10)

CCL9/CCL10，又称巨噬细胞炎症蛋白 1 γ (MIP-1γ)，巨噬细胞炎症蛋白相关蛋白 2 (MRP-2)，属于 CC 趋化因子家族的小细胞因子。CCL9/CCL10位于小鼠的11号染色体上，主要在巨噬细胞和骨髓细胞中组成型表达。 在 CC 趋化因子家族成员中，小鼠 CCL9 与小鼠 CCL6 (C10)、CCL3 (MIP-1α) 和 CCL4 (MIP-1β)的 aa 序列同源性分别为 45、24 和 20%。CCL9 可以与趋化因子细胞表面受体 CCR1 结合，参与破骨细胞的功能调节。CCL9/CCR1信号通路对髓系祖细胞向肠肿瘤的招募非常重要，从而导致肠肿瘤的侵袭增强。在 H22 肝癌模型中，脾巨噬细胞分泌的 CCL9 可以以 CCR1 依赖性方式诱导髓源性抑制细胞 (MDSC) 在脾脏中积累。此外，CCL9 在荷瘤小鼠的转移前肺或与肿瘤细胞共培养的未成熟髓系细胞中高度诱导，对肿瘤细胞在转移部位的存活起关键作用^[1][2][3]。

CCL9/CCL10, also known as macrophage inflammatory protein 1 γ (MIP-1γ) and macrophage inflammatory protein-related protein 2 (MRP-2), are small cytokines belonging to the CC chemokine family. CCL9/CCL10 are located on mouse chromosome 11 and are expressed constitutively mainly in macrophages and bone marrow cells. Among the CC chemokine family members, mouse CCL9 has 45, 24 and 20% aa sequence homology with mouse CCL6 (C10), CCL3 (MIP-1α) and CCL4 (MIP-1β), respectively. CCL9 can bind to the chemokine cell surface receptor CCR1 and is involved in the functional regulation of osteoclasts. The CCL9/CCR1 signaling pathway is important for the recruitment of myeloid progenitor cells to intestinal tumors, which leads to enhanced invasion of intestinal tumors. In the H22 hepatocellular carcinoma model, CCL9 secreted by splenic macrophages can induce the accumulation of myeloid-derived suppressor cells (MDSC) in the spleen in a CCR1-dependent manner. In addition, CCL9 is highly induced in pre-metastatic lungs of tumor-bearing mice or in immature myeloid cells co-cultured with tumor cells and plays a key role in the survival of tumor cells at metastatic sites^[1][2][3].

参考文献: