Influence of the interaction between nodal fibroblast and breast cancer cells on gene expression

Influence of the interaction between nodal fibroblast and breast cancer cells on gene expression
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DOI:
10.1007/s13277-010-0108-7
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发表时间:
2011-02-01
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影响因子:
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通讯作者:
Azevedo Koike Folgueira, Maria Aparecida
Azevedo Koike Folgueira, Maria Aparecida
中科院分区:
其他
文献类型:
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作者:
Costa Santos, Rosangela Portilho;Benvenuti, Ticiana Thomazine;Azevedo Koike Folgueira, Maria Aparecida

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我们的目的是评估乳腺癌细胞和结成纤维细胞之间的相互作用,通过他们的基因表达谱。从乳腺癌患者的阴性和阳性淋巴结建立成纤维细胞原代培养物,并在细胞培养后鉴定出相似的基因表达模式。将成纤维细胞和乳腺癌细胞(MDA-MB 231、MDA-MB 435和MCF 7)单独培养或通过多孔膜(其允许可溶性因子通过)分开共培养以进行比较。每个乳腺癌谱系对成纤维细胞活力和转录谱产生特定影响。然而,当与特定的乳腺癌细胞系共培养时,来自阳性和阴性淋巴结的成纤维细胞具有平行的转录行为。研究了淋巴结成纤维细胞对乳腺癌细胞的影响。MDA MB-231细胞活力和迁移通过成纤维细胞的存在而增强,因此,MDA-MB 435和MCF 7细胞活力遵循类似的模式。通过cDNA微阵列评估的MDA-MB 231基因表达谱受到成纤维细胞存在的影响,并且在一系列新的RT-PCR测定中,证实在MDA-MB 231与来自阴性和阳性淋巴结的成纤维细胞共培养的细胞中HNMT、COMT、FN 3 K和SOD 2下调。总之,乳腺癌细胞中由阳性和阴性淋巴结的成纤维细胞诱导的转录变化在特定谱系中非常相似。然而,成纤维细胞的影响是不同的,在每一个乳腺癌谱系,这表明基质和恶性细胞之间的相互关系是依赖于肿瘤的内在亚型。
Our aim was to evaluate the interaction between breast cancer cells and nodal fibroblasts, by means of their gene expression profile. Fibroblast primary cultures were established from negative and positive lymph nodes from breast cancer patients and a similar gene expression pattern was identified, following cell culture. Fibroblasts and breast cancer cells (MDA-MB231, MDA-MB435, and MCF7) were cultured alone or co-cultured separated by a porous membrane (which allows passage of soluble factors) for comparison. Each breast cancer lineage exerted a particular effect on fibroblasts viability and transcriptional profile. However, fibroblasts from positive and negative nodes had a parallel transcriptional behavior when co-cultured with a specific breast cancer cell line. The effects of nodal fibroblasts on breast cancer cells were also investigated. MDA MB-231 cells viability and migration were enhanced by the presence of fibroblasts and accordingly, MDA-MB435 and MCF7 cells viability followed a similar pattern. MDA-MB231 gene expression profile, as evaluated by cDNA microarray, was influenced by the fibroblasts presence, and HNMT, COMT, FN3K, and SOD2 were confirmed downregulated in MDA-MB231 co-cultured cells with fibroblasts from both negative and positive nodes, in a new series of RT-PCR assays. In summary, transcriptional changes induced in breast cancer cells by fibroblasts from positive as well as negative nodes are very much alike in a specific lineage. However, fibroblasts effects are distinct in each one of the breast cancer lineages, suggesting that the inter-relationships between stromal and malignant cells are dependent on the intrinsic subtype of the tumor.