CCL26 Participates in the PRL-3-Induced Promotion of Colorectal Cancer Invasion by Stimulating Tumor-Associated Macrophage Infiltration
CCL26 Participates in the PRL-3-Induced Promotion of Colorectal Cancer Invasion by Stimulating Tumor-Associated Macrophage Infiltration
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CCL26 通过刺激肿瘤相关巨噬细胞浸润参与 PRL-3 诱导的结直肠癌侵袭促进
DOI：
10.1158/1535-7163.mct-17-0507
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发表时间：
2018-01-01
影响因子：
5.7
通讯作者：
Chu, Zhonghua
中科院分区：
文献类型：
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作者：
Lan, Qiusheng;Lai, Wei;Chu, Zhonghua
再生肝磷酸酶-3（PRL-3）和肿瘤相关巨噬细胞（TAM）均影响癌症进展。PRL-3是否通过诱导TAM浸润在结直肠癌侵袭和转移中起关键作用尚不清楚。在目前的研究中，我们研究了趋化因子配体26（CCL 26）对TAM浸润和结直肠癌侵袭的影响，以及通过过表达或沉默PRL-3在结直肠癌细胞中的潜在机制。基因本体分析结果表明，PRL-3可上调CCL 26的表达，并参与细胞迁移。此外，IHC分析结果表明，PRL-3和CCL 26水平呈正相关，在III期和IV期结直肠癌组织中升高，并与结直肠癌患者的预后较差相关。此外，我们证明了CCL 26通过与CCR 3受体结合来诱导TAM浸润。当LoVo-P和HT 29-C细胞与TAM共培养时，CCL 26与CCR 3受体的结合通过动员TAM的细胞内Ca 2+增加IL 6和IL 8的表达来增强LoVo-P和HT 29-C细胞的侵袭力。此外，IHC结果表明，CCR 3蛋白水平和TAM计数在III期和IV期结直肠癌组织中较高，并与CCL 26相关。此外，使用注射LoVo-P和HT 29-C细胞的小鼠在体内观察到类似的结果。这些数据表明，PRL-3可能是一个潜在的预后标志物，通过上调CCL 26诱导TAM浸润，促进结直肠癌的侵袭和转移。Mol Cancer Ther; 17（1）; 276-89.©2017 AACR.
Both phosphatase of regenerating liver-3 (PRL-3) and tumor-associated macrophages (TAM) influence cancer progression. Whether PRL-3 plays a critical role in colorectal cancer invasion and metastasis by inducing TAM infiltration remains unclear. In the current study, we investigated the effects of chemokine ligand 26 (CCL26) on TAM infiltration and colorectal cancer invasion and the underlying mechanism in colorectal cancer cells by overexpressing or silencing PRL-3. We found that PRL-3 upregulated CCL26 expression correlatively and participated in cell migration, according to the results of gene ontology analysis. In addition, IHC analysis results indicated that the PRL-3 and CCL26 levels were positively correlated and elevated in stage III and IV colorectal cancer tissues and were associated with a worse prognosis in colorectal cancer patients. Furthermore, we demonstrated that CCL26 induced TAM infiltration by CCL26 binding to the CCR3 receptor. When LoVo-P and HT29-C cells were cocultured with TAMs, CCL26 binding to the CCR3 receptor enhanced the invasiveness of LoVo-P and HT29-C cells by mobilizing intracellular Ca2+of TAMs to increase the expression of IL6 and IL8. In addition, IHC results indicated that protein levels of CCR3 and TAMs counts were higher in stage III and IV colorectal cancer tissues and correlated with CCL26. Moreover, similar results were observed in vivo using mice injected with LoVo-P and HT29-C cells. These data indicate that PRL-3 may represent a potential prognostic marker that promotes colorectal cancer invasion and metastasis by upregulating CCL26 to induce TAM infiltration. Mol Cancer Ther; 17(1); 276–89. ©2017 AACR.