Interactome analysis of myeloid-derived suppressor cells in murine models of colon and breast cancer
Interactome analysis of myeloid-derived suppressor cells in murine models of colon and breast cancer
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DOI：
10.18632/oncotarget.2489
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发表时间：
2014-11-30
期刊：
影响因子：
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通讯作者：
Zhavoronkov, Alex
中科院分区：
文献类型：
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作者：
Aliper, Alexander M.;Frieden-Korovkina, Victoria P.;Zhavoronkov, Alex
在实体癌中，骨髓源性抑制细胞（MDSC）浸润肿瘤（周围）组织以诱导免疫耐受，从而建立允许肿瘤生长的微环境。重要的是，促进这种渗透或随后的免疫抑制的机制尚未完全了解。因此，在这项研究中，我们旨在描绘 MDSC 在结肠癌或乳腺癌小鼠模型中利用的不同分子途径。利用通路富集分析，我们完成了 c26GM 结肠癌小鼠脾脏和肿瘤浸润的 CD11b+/Gr1（高/低）MDSC 中多个信号通路的相互作用组图谱以及 4T1 乳腺癌 MDSC 的肿瘤浸润。在这两种癌症模型中，浸润性 MDSC（而非 CD11b+ 脾细胞）被发现富含多种信号分子，表明其增殖和侵袭表型增强。随后，相互作用组数据被用于重建之前未探索的通过分析预测的 c-myc 转录因子对 MDSC 细胞周期的调节。因此，这项研究代表了 MDSC 维持癌症进展的不同多种分子途径的首次相互作用组图谱。
In solid cancers, myeloid derived suppressor cells (MDSC) infiltrate (peri)tumoral tissues to induce immune tolerance and hence to establish a microenvironment permissive to tumor growth. Importantly, the mechanisms that facilitate such infiltration or a subsequent immune suppression are not fully understood. Hence, in this study, we aimed to delineate disparate molecular pathways which MDSC utilize in murine models of colon or breast cancer. Using pathways enrichment analysis, we completed interactome maps of multiple signaling pathways in CD11b+/Gr1(high/low) MDSC from spleens and tumor infiltrates of mice with c26GM colon cancer and tumor infiltrates of MDSC in 4T1 breast cancer. In both cancer models, infiltrating MDSC, but not CD11b+ splenic cells, have been found to be enriched in multiple signaling molecules suggestive of their enhanced proliferative and invasive phenotypes. The interactome data has been subsequently used to reconstruct a previously unexplored regulation of MDSC cell cycle by the c-myc transcription factor which was predicted by the analysis. Thus, this study represents a first interactome mapping of distinct multiple molecular pathways whereby MDSC sustain cancer progression.