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.
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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DOI：
10.18632/oncotarget.11931
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发表时间：
2016-10-18
期刊：
影响因子：
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通讯作者：
Pfeffer U
中科院分区：
文献类型：
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作者：
Amaro A;Angelini G;Mirisola V;Esposito AI;Reverberi D;Matis S;Maffei M;Giaretti W;Viale M;Gangemi R;Emionite L;Astigiano S;Cilli M;Bachmeier BE;Killian PH;Albini A;Pfeffer U
获得侵袭性表型是转移的先决条件，但目前尚不清楚侵袭性表型是否或在多大程度上与转移细胞的其他特征有关。我们从三阴性乳腺癌细胞系MDA-MB-231中选择了一个侵袭性亚群，通过Matrigel覆盖的膜进行重复的准备周期侵袭性检测。与亲本细胞相比，MDA-MB-231细胞的侵袭性亚群表现出更强的迁移能力，证实了所选细胞系的高侵袭性。长期培养这些细胞并不能消除侵袭性表型。ArrayCGH、DNA指数定量和核型分析证实了亲本和入侵亚群的共同遗传来源，并揭示了入侵亚群的离散结构差异，包括倍性增加和缺乏5p14.1-15.33染色体的特征扩增。基因表达分析显示，包括顶分泌性乳腺癌和侵袭相关的基质金属蛋白酶和细胞因子的特征在内的表达谱发生了显著变化。侵袭性细胞表现出加速的增殖、增加的凋亡率和改变的化疗敏感性模式，对影响有丝分裂装置的药物的IC50值较低。然而，在小鼠原位移植中，侵袭细胞群体的致瘤性显著降低，这表明获得侵袭能力和实现转移生长潜力是两个不同的事件。
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.