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首页> 美国卫生研究院文献>Oncotarget >A highly invasive subpopulation of MDA-MB-231 breast cancer cells shows accelerated growth differential chemoresistance features of apocrine tumors and reduced tumorigenicity in vivo
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A highly invasive subpopulation of MDA-MB-231 breast cancer cells shows accelerated growth differential chemoresistance features of apocrine tumors and reduced tumorigenicity in vivo

机译：MDA-MB-231乳腺癌细胞的高侵染性亚群在体内显示出加速的生长差异的化学耐药性顶泌性肿瘤的特征并降低了致瘤性

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The acquisition of an invasive phenotype is a prerequisite for metastasization, yet it is not clear whether or to which extent the invasive phenotype is linked to other features characteristic of metastatic cells. We selected an invasive subpopulation from the triple negative breast cancer cell line MDA-MB-231, performing repeated cycles of preparative assays of invasion through Matrigel covered membranes. The invasive sub-population of MDA-MB-231 cells exhibits stronger migratory capacity as compared to parental cells confirming the highly invasive potential of the selected cell line. Prolonged cultivation of these cells did not abolish the invasive phenotype. ArrayCGH, DNA index quantification and karyotype analyses confirmed a common genetic origin of the parental and invasive subpopulations and revealed discrete structural differences of the invasive subpopulation including increased ploidy and the absence of a characteristic amplification of chromosome 5p14.1-15.33. Gene expression analyses showed a drastically altered expression profile including features of apocrine breast cancers and of invasion related matrix-metalloproteases and cytokines. The invasive cells showed accelerated proliferation, increased apoptosis, and an altered pattern of chemo-sensitivity with lower IC50 values for drugs affecting the mitotic apparatus. However, the invasive cell population is significantly less tumorigenic in orthotopic mouse xenografts suggesting that the acquisition of the invasive capacity and the achievement of metastatic growth potential are distinct events.
机译：侵袭性表型的获得是转移的先决条件，但尚不清楚侵袭性表型是否与转移细胞的其他特征相关联或在何种程度上关联。我们从三阴性乳腺癌细胞系MDA-MB-231中选择了侵袭性亚群，对通过Matrigel覆盖膜进行的侵袭性制备测定进行了重复循环。与亲代细胞相比，MDA-MB-231细胞的侵袭性亚群表现出更强的迁移能力，这证实了所选细胞系的高度侵袭潜力。这些细胞的长期培养没有消除侵袭性表型。 ArrayCGH，DNA指数定量和核型分析证实了亲本和侵入性亚群的共同遗传起源，并揭示了侵入性亚群的离散结构差异，包括倍数性增加和染色体5p14.1-15.33的特征性扩增的缺失。基因表达分析表明表达谱发生了巨大变化，其中包括顶分泌乳腺癌的特征以及与侵袭有关的基质金属蛋白酶和细胞因子的特征。对于影响有丝分裂装置的药物，侵袭性细胞显示出加速的增殖，增加的凋亡和化学敏感性改变的模式，IC50值较低。但是，在原位小鼠异种移植物中，侵袭性细胞群的致瘤性明显降低，这表明侵袭能力的获得和转移性生长潜力的实现是不同的事件。

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