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Tumor-Stroma Interactions Alter the Sensitivity of Drug in Breast Cancer
Frontiers in Materials ( IF 2.6 ) Pub Date : 2020-04-15 , DOI: 10.3389/fmats.2020.00116
Virginia Brancato , Banani Kundu , Joaquim Miguel Oliveira , Vitor Manuel Correlo , Rui Luis Reis , Subhas C. Kundu

Flat cell cultures or xenografts are inadequate tools to unravel cancer complex biology. 3D in vitro tumor models garnered interest since they recapitulate better dynamic mechanisms of cancer, but a gold standard model that faithfully mimics solid cancer is not available yet. 3D breast cancer model is fabricated using freeze-dried silk fibroin scaffolds. Breast cancer cell lines (MCF-7 and MDA-MB231) are seeded with normal mammary fibroblasts onto silk fibroin scaffold (1 and 2 mm thick). Cells proliferation is monitored by means of Alamar blue assay. 3D breast cancer models morphology is observed by confocal microscopy. Gene expression modulation concerning extracellular matrix markers is evaluated. Further, 3D bioengineered breast cancer models are treated with doxorubicin. Silk fibroin scaffolds allow the proliferation of cancer cells and fibroblasts. Cells growth is enhanced when cancer cells and fibroblasts are seeded together. Histological staining shows 3D cell organization. MMP-1, MMP-2, MMP-3, Col-1, and Fibronectin expression is upregulated in co-culture. After doxorubicin treatment, stronger reduction in cell activity is observed in 2 mm SF scaffold in comparison to 1 mm. The 3D in vitro breast cancer model obtained can easily be scaled-up and translated to the preclinical testing of novel chemotherapeutics.



中文翻译:

肿瘤间质相互作用改变药物在乳腺癌中的敏感性。

扁平细胞培养或异种移植不足以解开癌症复杂的生物学工具。3D体外肿瘤模型引起了人们的兴趣,因为它们概括了更好的癌症动力学机制,但是还没有能够忠实模拟实体癌的金标准模型。使用冻干的丝素蛋白支架制造3D乳腺癌模型。将乳腺癌细胞系(MCF-7和MDA-MB231)与正常的乳腺成纤维细胞一起接种到丝素蛋白支架(1和2 mm厚)上。细胞增殖通过Alamar blue测定法监测。通过共聚焦显微镜观察到3D乳腺癌模型的形态。评价涉及细胞外基质标志物的基因表达调节。此外,用阿霉素治疗3D生物工程乳腺癌模型。丝素蛋白支架可以使癌细胞和成纤维细胞增殖。当癌细胞和成纤维细胞一起播种时,细胞的生长会增强。组织学染色显示3D细胞组织。在共培养中,MMP-1,MMP-2,MMP-3,Col-1和纤连蛋白的表达上调。阿霉素处理后,与1 mm相比,在2 mm SF支架中观察到更强的细胞活性降低。3D体外 获得的乳腺癌模型可以轻松扩大规模,并转化为新型化学疗法的临床前测试。

更新日期:2020-04-15
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