Nrf2 activation drive macrophages polarization and cancer cell epithelial-mesenchymal transition during interaction.
Nrf2 activation drive macrophages polarization and cancer cell epithelial-mesenchymal transition during interaction.
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DOI：
10.1186/s12964-018-0262-x
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发表时间：
2018-09-04
期刊：
影响因子：
--
通讯作者：
Shimada M
中科院分区：
文献类型：
--
作者：
Feng R;Morine Y;Ikemoto T;Imura S;Iwahashi S;Saito Y;Shimada M
肿瘤相关巨噬细胞（TAM）的M2表型可抑制抗肿瘤炎症、增加血管生成并促进肿瘤进展。转录因子核因子（红细胞衍生2）-样2（Nrf2）不仅调节血管生成，还通过抑制促炎细胞因子的表达发挥抗炎作用；然而，Nrf2 在癌细胞和巨噬细胞相互作用中的作用尚不清楚。将肝细胞癌细胞（Hep G2和Huh 7）和胰腺癌细胞（SUIT2和Panc-1）与单核细胞（THP-1）或外周血单核细胞来源的巨噬细胞共培养，然后检测巨噬细胞的表型变化和癌细胞的上皮间质转化。此外，还研究了 Nrf2 在癌细胞和巨噬细胞相互作用中的作用。在这项研究中，我们发现癌细胞可以诱导M2样巨噬细胞，其特征是通过Nrf2激活上调CD163和Arg1，下调IL-1b和IL-6。此外，巨噬细胞的 Nrf2 激活促进了 VEGF 表达。巨噬细胞的 Nrf2 激活与癌细胞衍生的乳酸诱导的活性氧相关。癌细胞培养的巨噬细胞可以激活癌细胞的 Nrf2，进而通过旁分泌 VEGF 增加癌细胞上皮间质转化 (EMT)。这些发现表明Nrf2在癌细胞和巨噬细胞的相互作用中发挥着重要作用。癌细胞源性乳酸对巨噬细胞 Nrf2 的激活使巨噬细胞偏向 M2 样表型，受教育的巨噬细胞激活癌细胞的 Nrf2，从而促进癌细胞的 EMT。这项研究提供了对 Nrf2 在癌细胞和 TAM 相互作用中的作用的新认识，并提出了潜在的治疗靶点。本文的在线版本 (10.1186/s12964-018-0262-x) 包含补充材料，可供授权用户使用。
The M2 phenotype of tumor-associated macrophages (TAM) inhibits the anti-tumor inflammation, increases angiogenesis and promotes tumor progression. The transcription factor Nuclear Factor (erythroid-derived 2)-Like 2 (Nrf2) not only modulates the angiogenesis but also plays the anti-inflammatory role through inhibiting pro-inflammatory cytokines expression; however, the role of Nrf2 in the cancer cell and macrophages interaction is not clear. Hepatocellular carcinoma cells (Hep G2 and Huh 7) and pancreatic cancer cells (SUIT2 and Panc-1) were co-cultured with monocytes cells (THP-1) or peripheral blood monocytes derived macrophages, then the phenotype changes of macrophages and epithelial-mesenchymal transition of cancer cells were detected. Also, the role of Nrf2 in cancer cells and macrophages interaction were investigated. In this study, we found that cancer cells could induce an M2-like macrophage characterized by up-regulation of CD163 and Arg1, and down-regulation of IL-1b and IL-6 through Nrf2 activation. Also, Nrf2 activation of macrophages promoted VEGF expression. The Nrf2 activation of macrophages correlated with the reactive oxygen species induced by cancer cells derived lactate. Cancer cells educated macrophages could activate Nrf2 of the cancer cells, in turn, to increase cancer cells epithelial-mesenchymal transition (EMT) through paracrine VEGF. These findings suggested that Nrf2 played the important role in the cancer cells and macrophages interaction. Macrophage Nrf2 activation by cancer cell-derived lactate skews macrophages polarization towards an M2-like phenotype and educated macrophages activate Nrf2 of the cancer cells to promote EMT of cancer cells. This study provides a new understanding of the role of Nrf2 in the cancer cell and TAM interaction and suggests a potential therapeutic target. The online version of this article (10.1186/s12964-018-0262-x) contains supplementary material, which is available to authorized users.
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影响因子：
3.6
作者：
Bobilev, Irene;Novik, Victoria;Danilenko, Michael
通讯作者：
Danilenko, Michael
肿瘤相关巨噬细胞的细胞和分子起源。
DOI：
10.1126/science.1252510
发表时间：
2014-05-23
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Franklin RA;Liao W;Sarkar A;Kim MV;Bivona MR;Liu K;Pamer EG;Li MO
通讯作者：
Li MO
影响因子：
2.8
作者：
Caronni, Nicoletta;Savino, Benedetta;Bonecchi, Raffaella
通讯作者：
Bonecchi, Raffaella
影响因子：
64.5
作者：
Chio IIC;Jafarnejad SM;Ponz-Sarvise M;Park Y;Rivera K;Palm W;Wilson J;Sangar V;Hao Y;Öhlund D;Wright K;Filippini D;Lee EJ;Da Silva B;Schoepfer C;Wilkinson JE;Buscaglia JM;DeNicola GM;Tiriac H;Hammell M;Crawford HC;Schmidt EE;Thompson CB;Pappin DJ;Sonenberg N;Tuveson DA
通讯作者：
Tuveson DA
影响因子：
9.2
作者：
Kuang L;Feng J;He G;Jing T
通讯作者：
Jing T