IL6 Mediates Immune and Colorectal Cancer Cell Cross-talk via miR-21 and miR-29b
IL6 Mediates Immune and Colorectal Cancer Cell Cross-talk via miR-21 and miR-29b
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DOI：
10.1158/1541-7786.mcr-15-0147
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发表时间：
2015-11-01
影响因子：
5.2
通讯作者：
Gooderham, Nigel J.
中科院分区：
文献类型：
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作者：
Patel, Saroor A. A.;Gooderham, Nigel J.
肿瘤被多种基质细胞类型包围和浸润，包括成纤维细胞、免疫细胞和血管内皮细胞，它们与恶性细胞相互作用产生肿瘤微环境（TME）。这种复杂的环境被认为受到肿瘤的调节，以促进其生存和进展，从而构成癌症治疗的潜在靶点。然而，微环境内的细胞间通讯尚不清楚。目前的研究利用体外共培养模型研究癌症和免疫细胞沟通的机制。研究表明，免疫细胞分泌的促炎细胞因子IL6可促进结直肠癌细胞的侵袭。此外，在IL6存在的情况下，癌细胞能够分泌循环miRNA miR-21和miR-29b，以进一步诱导免疫细胞产生IL6。还发现激活的免疫细胞将 miR-21 释放到 TME 中。总而言之，这些机制发现可以更好地理解 TME 中免疫细胞和癌细胞之间的细胞间通讯，并深入了解介导这种串扰的一些关键参与者。 意义：这项研究表明，共培养的癌症和免疫细胞通过 IL6 和循环 miRNA 进行通讯，以维持慢性炎症并促进前转移癌细胞行为。此外，还确定了介导 TME 中细胞间通讯的关键参与者，并提出了针对微环境的可能治疗方法。摩尔癌症研究中心； 13（11）； 1502-8。 (C) 2015 年 AACR。
Tumors are surrounded and infiltrated by a variety of stromal cell types, including fibroblasts, immune cells, and vascular endothelial cells, which interact with malignant cells to generate the tumor microenvironment (TME). This complex environment is thought to be regulated by the tumor in order to promote its survival and progression and thus constitutes a potential target for cancer therapy. However, intercellular communication within the microenvironment is not yet well understood. The current study investigates the mechanism by which cancer and immune cells communicate using an in vitro coculture model. It is demonstrated that IL6, a proinflammatory cytokine, secreted by immune cells promotes colorectal cancer cell invasiveness. In addition, in the presence of IL6, the cancer cells were able to secrete circulating miRNAs miR-21 and miR-29b to further induce immune cell IL6 production. Activated immune cells were also found to release miR-21 into the TME. Taken together, these mechanistic findings provide a better understanding of intercellular communication between immune and cancer cells in the TME and offer insight into some of the key players that mediate this cross-talk.Implications: This study demonstrates that cocultured cancer and immune cells communicate via IL6 and circulating miRNAs to sustain chronic inflammation and promote prometastatic cancer cell behavior. In addition, critical players are identified that mediate intercellular communication in the TME and suggest possible therapeutic approaches that target the microenvironment. Mol Cancer Res; 13(11); 1502-8. (C) 2015 AACR.