Rgs2 mediates pro-angiogenic function of myeloid derived suppressor cells in the tumor microenvironment via upregulation of MCP-1.
Rgs2 mediates pro-angiogenic function of myeloid derived suppressor cells in the tumor microenvironment via upregulation of MCP-1.
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DOI：
10.1371/journal.pone.0018534
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发表时间：
2011-04-11
期刊：
影响因子：
3.7
通讯作者：
Lin PC
中科院分区：
文献类型：
--
作者：
Boelte KC;Gordy LE;Joyce S;Thompson MA;Yang L;Lin PC
肿瘤生长与基质相互作用密切相关。骨髓源性抑制细胞（MDSC）在癌症患者和荷瘤小鼠中显著升高。MDSC通过减弱宿主免疫应答和增加血管化来调节肿瘤微环境。在寻找负责促肿瘤功能的分子介质时，我们发现与对照MDSC相比，G蛋白信号传导-2（Rgs 2）的调节因子在肿瘤源性MDSC中高度增加。我们进一步证明，缺氧，一个共同的特点与实体瘤，上调基因表达。小鼠中Rgs 2的基因缺失导致肿瘤生长的显著阻滞，并且肿瘤表现出血管密度降低和细胞死亡增加。有趣的是，MDSC中Rgs 2的缺失完全消除了它们的肿瘤促进功能，表明MDSC中的Rgs 2信号传导负责肿瘤促进功能。细胞因子阵列分析表明，Rgs 2 −/−肿瘤MDSC产生较少的MCP-1，导致血管生成减少，这可以通过添加重组MCP-1来恢复。我们的数据显示Rgs 2通过调节MCP-1的产生，作为肿瘤微环境中MDSC促血管生成功能的关键调节因子。
Tumor growth is intimately linked with stromal interactions. Myeloid derived suppressor cells (MDSCs) are dramatically elevated in cancer patients and tumor bearing mice. MDSCs modulate the tumor microenvironment through attenuating host immune response and increasing vascularization. In searching for molecular mediators responsible for pro-tumor functions, we found that regulator of G protein signaling-2 (Rgs2) is highly increased in tumor-derived MDSCs compared to control MDSCs. We further demonstrate that hypoxia, a common feature associated with solid tumors, upregulates the gene expression. Genetic deletion of Rgs2 in mice resulted in a significant retardation of tumor growth, and the tumors exhibit decreased vascular density and increased cell death. Interestingly, deletion of Rgs2 in MDSCs completely abolished their tumor promoting function, suggesting that Rgs2 signaling in MDSCs is responsible for the tumor promoting function. Cytokine array profiling identified that Rgs2−/− tumor MDSCs produce less MCP-1, leading to decreased angiogenesis, which could be restored with addition of recombinant MCP-1. Our data reveal Rgs2 as a critical regulator of the pro-angiogenic function of MDSCs in the tumor microenvironment, through regulating MCP-1 production.
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DOI：
10.1084/jem.184.2.569
发表时间：
1996-08-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Loetscher P;Seitz M;Baggiolini M;Moser B
通讯作者：
Moser B
影响因子：
64.5
作者：
Koelle, MR;Horvitz, HR
通讯作者：
Horvitz, HR
影响因子：
20.3
作者：
Schw채ble, J;Choudhary, C;Serve, H
通讯作者：
Serve, H
影响因子：
4.4
作者：
Sinha, Pratima;Clements, Virginia K.;Ostrand-Rosenberg, Suzanne
通讯作者：
Ostrand-Rosenberg, Suzanne
影响因子：
9.2
作者：
Siderovski, DP;Hessel, A;Tyers, M
通讯作者：
Tyers, M