Differential Content of Proteins, mRNAs, and miRNAs Suggests that MDSC and Their Exosomes May Mediate Distinct Immune Suppressive Functions.
Differential Content of Proteins, mRNAs, and miRNAs Suggests that MDSC and Their Exosomes May Mediate Distinct Immune Suppressive Functions.
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DOI：
10.1021/acs.jproteome.7b00646
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发表时间：
2018-01-05
影响因子：
4.4
通讯作者：
Fenselau C
中科院分区：
文献类型：
--
作者：
Geis-Asteggiante L;Belew AT;Clements VK;Edwards NJ;Ostrand-Rosenberg S;El-Sayed NM;Fenselau C
骨髓源性抑制细胞（MDSC）是未成熟的骨髓细胞，在大多数癌症患者的循环和肿瘤微环境中积累。在那里，MDSC 抑制适应性免疫和先天免疫，阻碍免疫治疗。癌症中经常存在的炎症环境促进 MDSC 抑制活性，导致肿瘤侵袭性进展和转移。荷瘤小鼠的 MDSC 释放外泌体，外泌体携带生物活性蛋白并介导 MDSC 的一些免疫抑制功能特征。对其他细胞类型的研究表明，外泌体也可能携带可转移到本地和远处细胞的 RNA，但迄今为止，尚未研究 MDSC 衍生的外泌体的 mRNA 和 microRNA 货物。在这里，对 MDSC 及其外泌体的货物进行了研究，目的是识别和表征可能促进 MDSC 抑制效力的分子。由于炎症是 MDSC 抑制活性的既定驱动力，因此我们使用了完善的 4T1 小鼠乳腺癌系统，其中包括“传统”和“炎症”MDSC。我们提供的证据表明，MDSC 衍生的外泌体携带的蛋白质、mRNA 和 microRNA 的定量特征与其亲本细胞不同。其中一些分子具有与 MDSC 抑制活性一致的已知或预测功能，表明潜在的机制冗余。
Myeloid-derived suppressor cells (MDSC) are immature myeloid cells that accumulate in the circulation and the tumor microenvironment of most cancer patients. There, MDSC suppress both adaptive and innate immunity, hindering immunotherapies. The inflammatory milieu often present in cancers facilitates MDSC suppressive activity, causing aggressive tumor progression and metastasis. MDSC from tumor-bearing mice release exosomes, which carry biologically active proteins and mediate some of the immunosuppressive functions characteristic of MDSC. Studies on other cell types have shown that exosomes may also carry RNAs which can be transferred to local and distant cells, yet the mRNA and microRNA cargo of MDSC-derived exosomes has not been studied to date. Here, the cargo of MDSC and their exosomes was interrogated with the goal of identifying and characterizing molecules that may facilitate MDSC suppressive potency. Because inflammation is an established driving force for MDSC suppressive activity, we used the well-established 4T1 mouse mammary carcinoma system, which includes “conventional” as well as “inflammatory” MDSC. We provide evidence that MDSC-derived exosomes carry proteins, mRNAs, and microRNAs with different quantitative profiles than that of their parental cells. Several of these molecules have known or predicted functions consistent with MDSC suppressive activity, suggesting a potential mechanistic redundancy.
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影响因子：
16
作者：
Crescitelli R;Lässer C;Szabó TG;Kittel A;Eldh M;Dianzani I;Buzás EI;Lötvall J
通讯作者：
Lötvall J
影响因子：
4.2
作者：
Chiba M;Kimura M;Asari S
通讯作者：
Asari S
影响因子：
5.5
作者：
Bunt, Stephanie K.;Clements, Virginia K.;Ostrand-Rosenberg, Suzanne
通讯作者：
Ostrand-Rosenberg, Suzanne
DOI：
10.1073/pnas.1209414109
发表时间：
2012-07-31
影响因子：
11.1
作者：
Fabbri, Muller;Paone, Alessio;Croce, Carlo M.
通讯作者：
Croce, Carlo M.
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y