Molecular characterization of the tumor microenvironment in breast cancer

Molecular characterization of the tumor microenvironment in breast cancer
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DOI:
10.1016/j.ccr.2004.06.010
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发表时间:
2004-07-01
期刊:
影响因子:
50.3
通讯作者:
Polyak, K
Polyak, K
中科院分区:
医学1区
文献类型:
--
作者:
Allinen, M;Beroukhim, R;Polyak, K

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在这里,我们描述了全面的基因表达谱的每种细胞类型组成的正常乳腺组织和原位和浸润性乳腺癌的基因表达的系列分析。基于这些数据,我们确定了在癌症进展期间所有细胞类型中都发生了广泛的基因表达变化,并且很大一部分改变的基因编码分泌蛋白和受体。尽管所有细胞类型中的基因表达发生了显著变化,但仅在癌上皮细胞中检测到遗传改变。分别在肿瘤肌上皮细胞和肌成纤维细胞中过表达的CXCL14和CXCL12趋化因子与上皮细胞上的受体结合并增强其增殖、迁移和侵袭。因此,趋化因子可能在乳腺肿瘤的发生中发挥作用,作为旁分泌因子。
Here we describe the comprehensive gene expression profiles of each cell type composing normal breast tissue and in situ and invasive breast carcinomas using serial analysis of gene expression. Based on these data, we determined that extensive gene expression changes occur in all cell types during cancer progression and that a significant fraction of altered genes encode secreted proteins and receptors. Despite the dramatic gene expression changes in all cell types, genetic alterations were detected only in cancer epithelial cells. The CXCL14 and CXCL12 chemokines overexpressed in tumor myoepithelial cells and myofibroblasts, respectively, bind to receptors on epithelial cells and enhance their proliferation, migration, and invasion. Thus, chemokines may play a role in breast tumorigenesis by acting as paracrine factors.