Tumor-Stroma Interactions Alter the Sensitivity of Drug in Breast Cancer
Tumor-Stroma Interactions Alter the Sensitivity of Drug in Breast Cancer
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DOI：
10.3389/fmats.2020.00116
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发表时间：
2020-06-25
影响因子：
3.2
通讯作者：
Kundu, Subhas C.
中科院分区：
文献类型：
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作者：
Brancato, Virginia;Kundu, Banani;Kundu, Subhas C.
扁平细胞培养或异种移植是不足以解开癌症复杂生物学的工具。3D体外肿瘤模型引起了人们的兴趣，因为它们概括了癌症的更好的动态机制，但是忠实地模拟实体癌的金标准模型还没有。采用冻干丝素蛋白支架构建乳腺癌三维模型。将乳腺癌细胞系（MCF-7和MDA-MB 231）与正常乳腺成纤维细胞一起接种到丝纤蛋白支架（1和2 mm厚）上。细胞增殖通过阿利兰测定法监测。利用共聚焦显微镜观察乳腺癌三维模型的形态。评价关于细胞外基质标志物的基因表达调节。此外，3D生物工程乳腺癌模型用阿霉素治疗。丝素蛋白支架允许癌细胞和成纤维细胞增殖。当癌细胞和成纤维细胞接种在一起时，细胞生长增强。组织学染色显示3D细胞组织。MMP-1、MMP-2、MMP-3、Col-1和纤连蛋白表达在共培养中上调。多柔比星治疗后，更强的细胞活性的减少，观察到在2毫米SF支架相比，1毫米。获得的3D体外乳腺癌模型可以很容易地扩大规模，并转化为新的化疗药物的临床前测试。
Flat cell cultures or xenografts are inadequate tools to unravel cancer complex biology. 3Din vitrotumor 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 3Din vitrobreast cancer model obtained can easily be scaled-up and translated to the preclinical testing of novel chemotherapeutics.