TGFβ signaling in myeloid cells regulates mammary carcinoma cell invasion through fibroblast interactions.
TGFβ signaling in myeloid cells regulates mammary carcinoma cell invasion through fibroblast interactions.
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DOI：
10.1371/journal.pone.0117908
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Novitskiy SV
中科院分区：
文献类型：
--
作者：
Shaw AK;Pickup MW;Chytil A;Aakre M;Owens P;Moses HL;Novitskiy SV
转移是癌症最具破坏性的方面，然而我们对转移的最早阶段--局部浸润的机制知之甚少。在肿瘤生长过程中，CD 11b + Gr 1+细胞（也称为MDSC）已被证明通过抑制抗肿瘤免疫应答的广谱效应促进肿瘤进展。除了免疫抑制，CD 11b + Gr 1+细胞通过目前未知的机制促进转移。CD 11b + Gr 1+细胞定位于成纤维细胞附近，其重塑ECM并为癌细胞的集体细胞迁移留下轨迹。在这项研究中，我们发现，CD 11b + Gr 1+细胞通过增加成纤维细胞迁移促进乳腺癌细胞的侵袭。这种作用是由CD 11b + Gr 1+细胞分泌的因子指导的。我们已经鉴定了几种激活成纤维细胞迁移的CD 11b + Gr 1+细胞分泌蛋白，包括CXCL 11、CXCL 15、FGF 2、IGF-I、IL 1 Ra、Resistin和Shh。CXCL 11和FGF 2的组合对与Akt 1和ERK 1/2磷酸化相关的成纤维细胞迁移具有最强的作用。对CD 11b + Gr 1+细胞亚群的分析表明，CD 11b + Ly 6ChighLy 6 Glow细胞比其他髓系细胞群更能增加成纤维细胞迁移。此外，肿瘤来源的CD 11b + Gr 1+细胞比荷瘤小鼠的脾脏CD 11b + Gr 1+细胞更能促进成纤维细胞迁移。虽然成纤维细胞中的TGFβ信号传导不调节其向CD 11b + Gr 1+细胞的迁移，但是CD 11b + Gr 1+细胞上的TGFβ受体II的缺失下调CXCL 11、Shh、IGF 1和FGF 2，导致成纤维细胞迁移减少。这些研究表明，CD 11b + Gr 1+细胞中的TGFβ信号促进成纤维细胞定向的癌侵袭，并表明血管周围的CD 11b + Ly 6ChighLy 6 Glow细胞可能是导致转移的局部侵袭的刺激物。
Metastasis is the most devastating aspect of cancer, however we know very little about the mechanisms of local invasion, the earliest step of metastasis. During tumor growth CD11b+Gr1+ cells, known also as MDSCs, have been shown to promote tumor progression by a wide spectrum of effects that suppress the anti-tumor immune response. In addition to immunosuppression, CD11b+Gr1+ cells promote metastasis by mechanisms that are currently unknown. CD11b+Gr1+ cells localize near fibroblasts, which remodel the ECM and leave tracks for collective cell migration of carcinoma cells. In this study we discovered that CD11b+Gr1+ cells promote invasion of mammary carcinoma cells by increasing fibroblast migration. This effect was directed by secreted factors derived from CD11b+Gr1+ cells. We have identified several CD11b+Gr1+ cell secreted proteins that activate fibroblast migration, including CXCL11, CXCL15, FGF2, IGF-I, IL1Ra, Resistin, and Shh. The combination of CXCL11 and FGF2 had the strongest effect on fibroblast migration that is associated with Akt1 and ERK1/2 phosphorylation. Analysis of subsets of CD11b+Gr1+ cells identified that CD11b+Ly6ChighLy6Glow cells increase fibroblast migration more than other myeloid cell populations. Additionally, tumor-derived CD11b+Gr1+ cells promote fibroblast migration more than splenic CD11b+Gr1+ cells of tumor-bearing mice. While TGFβ signaling in fibroblasts does not regulate their migration toward CD11b+Gr1+ cells, however deletion of TGFβ receptor II on CD11b+Gr1+ cells downregulates CXCL11, Shh, IGF1 and FGF2 resulting in reduced fibroblast migration. These studies show that TGFβ signaling in CD11b+Gr1+ cells promotes fibroblast directed carcinoma invasion and suggests that perivascular CD11b+Ly6ChighLy6Glow cells may be the stimulus for localized invasion leading to metastasis.
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影响因子：
1.5
作者：
Chytil, A;Magnuson, MA;Moses, HL
通讯作者：
Moses, HL
影响因子：
5.3
作者：
Mognetti B;La Montagna G;Perrelli MG;Pagliaro P;Penna C
通讯作者：
Penna C
影响因子：
32.4
作者：
Marie, Julien C.;Liggitt, Denny;Rudensky, Alexander Y.
通讯作者：
Rudensky, Alexander Y.
影响因子：
5.5
作者：
Novitskiy, Sergey V.;Pickup, Michael W.;Moses, Harold L.
通讯作者：
Moses, Harold L.
DOI：
10.1084/jem.187.12.2009
发表时间：
1998-06-15
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Cole KE;Strick CA;Paradis TJ;Ogborne KT;Loetscher M;Gladue RP;Lin W;Boyd JG;Moser B;Wood DE;Sahagan BG;Neote K
通讯作者：
Neote K