Association of changes in the gene expression profile of blood cells with the local tumor inflammatory response in a murine tumor model
Association of changes in the gene expression profile of blood cells with the local tumor inflammatory response in a murine tumor model
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DOI：
10.1016/j.bbrc.2012.10.004
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发表时间：
2012-11-09
影响因子：
3.1
通讯作者：
Kaneko, Shuichi
中科院分区：
文献类型：
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作者：
Sakai, Yoshio;Tatsumi, Isamu;Kaneko, Shuichi
癌症组织经常与宿主的炎症反应有关，后者涉及血细胞。利用DNA芯片，我们检测了小鼠皮下肝癌模型中血液和肿瘤的基因表达谱，在该模型中，肿瘤在最初的10天内发展，然后在植入后第25天消退和消失。免疫组织化学和基因表达分析表明，第10天肿瘤组织出现主动免疫反应，尤其是CD4+T细胞介导的免疫反应。第10天血液中普遍上调的基因和富含肿瘤相关炎症细胞的部分也表明CD4+T细胞参与其中。对第0、10、15、20和25天外周血细胞基因表达的非监督等级聚类分析表明，主要有两个聚类群：第10、15和20天的有肿瘤聚集群，以及0和25天的无肿瘤聚集群。此外，每天都会检测到子星团。这些结果表明，全血细胞的基因表达谱受局部肿瘤状况的影响，并与局部宿主的免疫反应有关。它的分析将有助于探索宿主对肿瘤免疫反应的潜在重要特征。(C)2012 Elsevier Inc.保留所有权利。
Cancer tissue is frequently associated with the host inflammatory response, which involves blood cells. Using DNA microarrays, we examined the gene expression profiles of blood and tumors in a murine subcutaneous hepatocellular carcinoma model, in which tumors develop during the initial 10 days and then diminish and disappear by day 25 after implantation. Immunohistochemical and gene expression analysis indicated that tumor tissues were associated with an active immune response, particularly the CD4+ T cell-mediated immune response, on day 10. The genes commonly up-regulated in blood and the fraction enriched with tumor-associated inflammatory cells on day 10 also suggested the involvement of CD4+ T cells. Unsupervised hierarchical clustering analysis of gene expression of peripheral blood cells on days 0, 10, 15, 20, and 25 indicated two major clusters: the tumor-existence cluster on days 10, 15, and 20, and the tumor-free cluster on days 0 and 25. Additionally, sub-clusters were detected on each day. These results suggest that the gene expression profile of whole blood cells is affected by the local tumor condition, and is associated with the local host immune response. Its analysis will facilitate exploration of the underlying important features of the host immune response to tumors. (C) 2012 Elsevier Inc. All rights reserved.