Transcriptomic analysis comparing tumor-associated neutrophils with granulocytic myeloid-derived suppressor cells and normal neutrophils.

Transcriptomic analysis comparing tumor-associated neutrophils with granulocytic myeloid-derived suppressor cells and normal neutrophils.
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DOI:
10.1371/journal.pone.0031524
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Albelda SM
Albelda SM
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Fridlender ZG;Sun J;Mishalian I;Singhal S;Cheng G;Kapoor V;Horng W;Fridlender G;Bayuh R;Worthen GS;Albelda SM

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骨髓细胞在支持癌症生长中的作用已经得到充分证实。大多数工作都集中在骨髓来源的抑制细胞(MDSC),积累在荷瘤动物,但肿瘤相关的中性粒细胞(TAN)也被认为是能够增加肿瘤的生长。然而,很少有人知道他们的演变,表型,并与幼稚中性粒细胞(NN)和粒细胞部分的MDSC(G-MDSC)的关系。在目前的研究中,在小鼠中使用转录组学方法来比较这些细胞类型。我们的数据表明,这三个群体的中性粒细胞是显着不同的,在他们的mRNA谱与NN和G-MDSC是更密切相关的彼此比TAN。在TAN中,结构基因和细胞毒性相关基因(即呼吸爆发)显著下调。相反,许多免疫相关基因和途径,包括与抗原呈递复合物相关的基因(例如所有六种MHC-II复合物基因)和细胞因子(例如TNF-α、IL-1-α/β),在G-MDSC中上调,并在TAN中进一步上调。与NN相比,测试的25种趋化因子中有13种在TAN中显著上调,包括T/B细胞、中性粒细胞和巨噬细胞的趋化因子的显著上调。本研究描述了与癌症相关的不同嗜中性粒细胞群体的特征,指出了TAN与其他嗜中性粒细胞群体之间的主要差异。
The role of myeloid cells in supporting cancer growth is well established. Most work has focused on myeloid-derived suppressor cells (MDSC) that accumulate in tumor-bearing animals, but tumor-associated neutrophils (TAN) are also known to be capable of augmenting tumor growth. However, little is known about their evolution, phenotype, and relationship to naïve neutrophils (NN) and to the granulocytic fraction of MDSC (G-MDSC). In the current study, a transcriptomics approach was used in mice to compare these cell types. Our data show that the three populations of neutrophils are significantly different in their mRNA profiles with NN and G-MDSC being more closely related to each other than to TAN. Structural genes and genes related to cell-cytotoxicity (i.e. respiratory burst) were significantly down-regulated in TAN. In contrast, many immune-related genes and pathways, including genes related to the antigen presenting complex (e.g. all six MHC-II complex genes), and cytokines (e.g. TNF-α, IL-1-α/β), were up-regulated in G-MDSC, and further up-regulated in TAN. Thirteen of the 25 chemokines tested were markedly up-regulated in TAN compared to NN, including striking up-regulation of chemoattractants for T/B-cells, neutrophils and macrophages. This study characterizes different populations of neutrophils related to cancer, pointing out the major differences between TAN and the other neutrophil populations.
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影响因子: 4.6
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