TRIB1 通过抑制前列腺癌细胞中的 IKB-zeta 诱导巨噬细胞向 M2 表型转化。
TRIB1 induces macrophages to M2 phenotype by inhibiting IKB-zeta in prostate cancer.
机构信息
Department of Urology, Huadu District People's Hospital, Southern Medical University, Guangzhou 510800, China; Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou 510180, China; Guangdong Provincial Institute of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou 510180, China.
出版信息
Cell Signal. 2019 Jul;59:152-162. doi: 10.1016/j.cellsig.2019.03.017. Epub 2019 Mar 26.
Immunotherapy has made great breakthroughs in the field of cancer. However, the immunotherapeutic effect of prostate cancer is unsatisfactory. We found that the expression of TRIB1 was significantly correlated with the infiltration of CD163+ macrophages in prostate cancer. This study focused on the effects of TRIB1 on macrophage polarization in the immune microenvironment of prostate cancer. RNA sequencing analysis demonstrated that TRIB1 has significant effects on the regulation of the nuclear factor (NF)-κB signaling pathway and downstream cytokines. Flow cytometry and enzyme-linked immunosorbent assay were used to examine THP-1 cells cultured in conditioned medium from prostate cancer cells overexpressing TRIB1 and showed that overexpression of TRIB1 promoted the secretion of CXCL2 and interleukin (IL)8 by PC3 cells, which increased the secretion of IL12 by THP-1 cells as well as the expression of CD163 on THP-1 cells. IKB-zeta, regulated by TRIB1, was expressed in PC3 cells but was barely detectable in DU145 cells. The reductions in CXCL2 and IL8 by the inhibition of TRIB1 were rescued by the deletion of IKB-zeta. Here we showed that TRIB1 promoted the secretion of cytokines from prostate cancer cells and induced the differentiation of monocytes/macrophages into M2 macrophages.
免疫疗法在癌症领域取得了重大突破。然而，前列腺癌的免疫治疗效果并不理想。我们发现 TRIB1 的表达与前列腺癌中 CD163+巨噬细胞的浸润显著相关。本研究重点探讨了 TRIB1 对前列腺癌免疫微环境中巨噬细胞极化的影响。RNA 测序分析表明，TRIB1 对核因子 (NF)-κB 信号通路及其下游细胞因子的调控具有显著影响。流式细胞术和酶联免疫吸附试验检测了过表达 TRIB1 的前列腺癌细胞条件培养基中培养的 THP-1 细胞，结果表明，TRIB1 的过表达促进了 PC3 细胞分泌 CXCL2 和白细胞介素 (IL)-8，这也增加了 THP-1 细胞分泌的 IL12 以及 THP-1 细胞上 CD163 的表达。受 TRIB1 调控的 IKB-zeta 在 PC3 细胞中表达，但在 DU145 细胞中几乎检测不到。TRIB1 抑制后 CXCL2 和 IL8 的减少被 IKB-zeta 的缺失所挽救。本研究表明，TRIB1 促进了前列腺癌细胞分泌细胞因子，并诱导单核细胞/巨噬细胞向 M2 巨噬细胞分化。
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