Biological characteristics and genetic heterogeneity between carcinoma-associated fibroblasts and their paired normal fibroblasts in human breast cancer.
Biological characteristics and genetic heterogeneity between carcinoma-associated fibroblasts and their paired normal fibroblasts in human breast cancer.
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DOI：
10.1371/journal.pone.0060321
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Liu M
中科院分区：
文献类型：
--
作者：
Peng Q;Zhao L;Hou Y;Sun Y;Wang L;Luo H;Peng H;Liu M
基质细胞和肿瘤细胞之间的串扰中的延伸信号由细胞外基质分子、可溶性因子和细胞-细胞粘附复合物产生，在肿瘤微环境中在细胞外和细胞内水平上合作。CAFs是肿瘤微环境中的主要基质细胞类型，在肿瘤的发生和发展中起着关键作用。然而，CAFs的功能与其异常信号通路之间的内在联系还缺乏系统的分析。CAFs的特征及其在肿瘤发生发展中的作用的极端复杂性需要进一步研究。我们原代培养了早期乳腺癌组织中的CAFs和NFs，并通过免疫组织化学方法对其进行了鉴定，包括纤维连接蛋白、α-SMA和FAP。应用基因芯片技术分析人乳腺CAFs及配对NF的基因表达谱。通过Gene Ontology对上调基因进行分类，通过大卫通路分析对信号通路进行富集。乳腺癌CAFs中的异常信号通路涉及细胞周期、细胞粘附、信号转导和蛋白质转运，在其他肿瘤来源的CAFs中也有报道。值得注意的是，改变的ATM信号通路，一组细胞周期调节的信号，和免疫相关的信号被确定为在CAFs中改变。与NF相比，CAFs具有较强的增殖能力和侵袭迁移能力。CAFs可通过上调CCL 18和CXCL 12的表达促进乳腺癌细胞在共培养条件下的侵袭。基因表达谱分析结果表明，细胞周期、细胞粘附、分泌因子等信号通路在CAFs中起着重要作用，这与CAFs的生物学行为一致。改变的ATM信号通路在乳腺癌的早期阶段异常活跃。这组免疫相关信号可能参与肿瘤细胞的免疫逃避。
The extensional signals in cross-talk between stromal cells and tumor cells generated from extracellular matrix molecules, soluble factor, and cell-cell adhesion complexes cooperate at the extra- and intracellular level in the tumor microenvironment. CAFs are the primary type of stromal cells in the tumor microenvironment and play a pivotal role in tumorigenesis and development. Hitherto, there is hardly any systematic analysis of the intrinsic relationship between CAFs function and its abnormal signaling pathway. The extreme complexity of CAFs’ features and their role in tumor development are needed to be further investigated. We primary cultured CAFs and NFs from early stages of breast cancer tissue and identified them using their biomarker by immunohistochemistry for Fibronectin, α-SMA and FAP. Microarray was applied to analyze gene expression profiles of human breast CAFs and the paired NFs. The Up-regulated genes classified by Gene Ontology, signal pathways enriched by DAVID pathway analysis. Abnormal signaling pathways in breast cancer CAFs are involved in cell cycle, cell adhesion, signal transduction and protein transport being reported in CAFs derived from other tumors. Significantly, the altered ATM signaling pathway, a set of cell cycle regulated signaling, and immune associated signaling are identified to be changed in CAFs. CAFs have the vigorous ability of proliferation and potential of invasion and migration comparing with NFs. CAFs could promote breast cancer cell invasion under co-culture conditions through up-regulated CCL18 and CXCL12. Consistently with its biologic behavior, the gene expression profiling analyzed by microarray shows that some of key signaling pathways, such as cell cycle, cell adhesion, and secreting factors play an important role in CAFs. The altered ATM signaling pathway is abnormally active in the early stage of breast cancer. The set of immune associated signaling may be involved in tumor cell immune evasion.
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影响因子：
37.3
作者：
Haubeiss S;Schmid JO;Mürdter TE;Sonnenberg M;Friedel G;van der Kuip H;Aulitzky WE
通讯作者：
Aulitzky WE
影响因子：
3.7
作者：
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Ngan HY
影响因子：
14.9
作者：
Draghici, S;Khatri, P;Tainsky, MA
通讯作者：
Tainsky, MA
影响因子：
0.9
作者：
Jacob, Theresa;Hingorani, Anil;Ascher, Enrico
通讯作者：
Ascher, Enrico
影响因子：
11.2
作者：
Huang C;Qiu Z;Wang L;Peng Z;Jia Z;Logsdon CD;Le X;Wei D;Huang S;Xie K
通讯作者：
Xie K