Proteomic Comparison of MCF-7 Tumoursphere and Monolayer Cultures
Proteomic Comparison of MCF-7 Tumoursphere and Monolayer Cultures
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DOI：
10.1371/journal.pone.0052692
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发表时间：
2012-12-20
期刊：
影响因子：
3.7
通讯作者：
Lopez, J. Alejandro
中科院分区：
文献类型：
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作者：
Morrison, Brian J.;Hastie, Marcus L.;Lopez, J. Alejandro
乳腺癌是一种异质性疾病，由具有不同基因表达和表型的肿瘤细胞组成。很少有抗原已被确定和更好地了解肿瘤起始细胞作为治疗的目标是迫切需要的。最近，已经描述了肿瘤内的罕见细胞亚群具有以下能力：（i）启动和维持肿瘤生长;（ii）抵抗传统疗法并允许继发性肿瘤传播;以及（iii）显示干细胞的一些特征，例如自我更新。这些细胞被称为肿瘤起始细胞或癌症干细胞，或者在乳腺癌的情况下，称为乳腺癌干细胞。以前的研究已经证明，乳腺癌干细胞可以在“肿瘤球”培养中富集。蛋白质组学是研究细胞间蛋白质表达的一种新方法。我们假设，与粘附/分化细胞相比，乳腺癌细胞系MCF-7肿瘤球的蛋白质组的表征鉴定了用于进一步分离或靶向乳腺癌干细胞的新的感兴趣的蛋白质。我们提出的证据表明：（i）贴壁细胞的蛋白质组不同于在球形培养基中生长的细胞的蛋白质组，（第2代）或晚期传代（第5代）球体;（ii）球体富含多种肿瘤相关蛋白的表达（包括MUC 1和半乳糖凝集素-3）;和（iii）这些鉴定的蛋白质之一的靶向使用抑制剂（N-乙酰乳糖胺）的半乳糖凝集素-3（galectin-3）在体外降低MCF-7癌症干细胞的球体形成/自我更新和在体内降低致瘤性。因此，肿瘤球的蛋白质组学分析可能会发现用于确定未来治疗的新靶点。乳腺癌干细胞是一种高度临床相关的肿瘤细胞亚群，其治疗靶向具有消除残留疾病的潜力，并可能成为癌症多模式治疗的重要组成部分。
Breast cancer is a heterogenous disease, composed of tumour cells with differing gene expressions and phenotypes. Very few antigens have been identified and a better understanding of tumour initiating-cells as targets for therapy is critically needed. Recently, a rare subpopulation of cells within tumours has been described with the ability to: (i) initiate and sustain tumour growth; (ii) resist traditional therapies and allow for secondary tumour dissemination; and (iii) display some of the characteristics of stem cells such as self-renewal. These cells are termed tumour-initiating cells or cancer stem cells, or alternatively, in the case of breast cancer, breast cancer stem cells. Previous studies have demonstrated that breast cancer stem cells can be enriched for in "tumoursphere" culture. Proteomics represents a novel way to investigate protein expression between cells. We hypothesise that characterisation of the proteome of the breast cancer line MCF-7 tumourspheres compared to adherent/differentiated cells identifies proteins of novel interest for further isolating or targeting breast cancer stem cells. We present evidence that: (i) the proteome of adherent cells is different to the proteome of cells grown in sphere medium from either early passage (passage 2) or late passage (passage 5) spheres; (ii) that spheres are enriched in expression of a variety of tumour-relevant proteins (including MUC1 and Galectin-3); and (iii) that targeting of one of these identified proteins (galectin-3) using an inhibitor (N-acetyllactosamine) decreases sphere formation/self-renewal of MCF-7 cancer stem cells in vitro and tumourigenicity in vivo. Hence, proteomic analysis of tumourspheres may find use in identifying novel targets for future therapy. The therapeutic targeting of breast cancer stem cells, a highly clinically relevant sub-population of tumour cells, has the potential to eliminate residual disease and may become an important component of a multi-modality treatment of cancer.