Characterization of the MDSC proteome associated with metastatic murine mammary tumors using label-free mass spectrometry and shotgun proteomics.
Characterization of the MDSC proteome associated with metastatic murine mammary tumors using label-free mass spectrometry and shotgun proteomics.
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DOI：
10.1371/journal.pone.0022446
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发表时间：
2011
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：
Boutté AM;McDonald WH;Shyr Y;Yang L;Lin PC
Gr-1+/CD 11b+髓源性抑制细胞（MDSC）的扩增受转移性、恶性原发性肿瘤增加的影响。转移，而不是原发肿瘤，往往是死亡的原因。本研究试图在具有来自相同肿瘤的肿瘤细胞系67 NR和4 T1的小鼠模型中，使用无标记质谱鸟枪蛋白质组学来充分表征MDSC蛋白质组对转移性和非转移性乳腺肿瘤的响应。67 NR细胞仅形成原发性乳腺肿瘤，而4 T1细胞容易转移到肺、淋巴结和血液。总体分析鉴定了总共2825个蛋白质组，错误发现率为0.78%。在2814个真鉴定中，43个蛋白质专属于67 NR组，153个蛋白质专属于4 T1组，2618个蛋白质共有。在共享队列中，与非转移性67 NR对照相比，过滤后转移性4 T1队列中有26种蛋白质增加，31种蛋白质减少。MDSC选择性表达参与γ-谷氨酰转移酶、谷胱甘肽合成酶途径、CREB转录因子信号传导和参与血小板聚集的其他途径以及脂质和氨基酸代谢的蛋白质，以响应高转移性4 T1肿瘤。细胞周期调控主导的蛋白质途径和本体组的67 NR非转移组。这项研究不仅提供了一个起点，以确定MDSC表达的转移的潜在生物标志物;它确定了非转移性和转移性疾病特有的关键途径。针对MDSC中这些通路的治疗干预可能为控制恶性肿瘤和转移提供新的途径。
Expansion of Gr-1+/CD11b+ myeloid derived suppressor cells (MDSCs) is governed by the presence of increasingly metastatic, malignant primary tumors. Metastasis, not the primary tumor, is often the cause of mortality. This study sought to fully characterize the MDSC proteome in response to metastatic and non-metastatic mammary tumors using label-free mass spectrometry shotgun proteomics in a mouse model with tumor cell lines, 67NR and 4T1, derived from the same tumor. 67NR cells form only primary mammary tumors, whereas 4T1 cells readily metastasize to the lungs, lymph nodes, and blood. Overall analysis identified a total of 2825 protein groups with a 0.78% false discovery rate. Of the 2814 true identifications, 43 proteins were exclusive to the 67NR group, 153 were exclusive to the 4T1 group, and 2618 were shared. Among the shared cohort, 26 proteins were increased and 31 were decreased in the metastatic 4T1 cohort compared to non-metastatic 67NR controls after filtering. MDSCs selectively express proteins involved in the γ-glutamyl transferase, glutathione synthase pathways, CREB transcription factor signaling, and other pathways involved in platelet aggregation, as well as lipid and amino acid metabolism, in response to highly metastatic 4T1 tumors. Cell cycle regulation dominated protein pathways and ontological groups of the 67NR non-metastatic group. Not only does this study provide a starting point to identify potential biomarkers of metastasis expressed by MDSCs; it identifies critical pathways that are unique to non-metastatic and metastatic conditions. Therapeutic interventions aimed at these pathways in MDSC may offer a new route to control malignancy and metastasis.
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