School of Materials Science and Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore, 639798, Singapore.
Biological Sciences and Technology Division, Biotechnology Group, CSIR-North East Institute of Science & Technology, Academy of Scientific and Innovative Research, Jorhat, Assam, 785006, India.
Sci Rep. 2019 Jun 20;9(1):8997. doi: 10.1038/s41598-019-45384-9.
Cancer cells undergoing epithelial-mesenchymal transition (EMT) acquire stem cell-like phenotype associated with malignant behaviour, chemoresistance, and relapse. Current two-dimensional (2D) in-vitro culture models of tumorigenesis are inadequate to replicate the complexity of in-vivo microenvironment. Therefore, the generation of functional three-dimensional (3D) constructs is a fundamental prerequisite to form multi-cellular tumour spheroids for studying basic pathological mechanisms. In this study, we focused on two major points (i) designing and fabrication of 3D hybrid scaffolds comprising electrospun fibers with cancer cells embedded within hydrogels, and (ii) determining the potential roles of 3D hybrid scaffolds associated with EMT in cancer progression and metastasis. Our findings revealed that 3D hybrid scaffold enhances cell proliferation and induces cancer cells to undergo EMT, as demonstrated by significant up-regulation of EMT associated transcriptional factors including Snail1, Zeb1, and Twist2; and mesenchymal markers whereas epithelial marker, E-Cadherin was downregulated. Remarkably, this induction is independent of cancer cell-type as similar results were obtained for breast cancer cells, MDA-MB-231 and gastric cancer cells, MKN74. Moreover, the hybrid scaffolds enrich aggressive cancer cells with stem cell properties. We showed that our 3D scaffolds could trigger EMT of cancer cells which could provide a useful model for studying anticancer therapeutics against metastasis.
癌细胞在经历上皮-间充质转化（EMT）后获得与恶性行为、化疗耐药和复发相关的干细胞样表型。目前肿瘤发生的二维（2D）体外培养模型不足以复制体内微环境的复杂性。因此，生成功能性三维（3D）结构是形成用于研究基本病理机制的多细胞肿瘤球体的基本前提。在这项研究中，我们重点关注两个主要方面：（i）设计和制造包含嵌入水凝胶中的癌细胞的 3D 杂交支架的纤维，（ii）确定与 EMT 相关的 3D 杂交支架在癌症进展和转移中的潜在作用。我们的研究结果表明，3D 杂交支架可增强细胞增殖并诱导癌细胞经历 EMT，这表现为 EMT 相关转录因子（包括 Snail1、Zeb1 和 Twist2）和间充质标志物的显著上调，而上皮标志物 E-钙粘蛋白则下调。值得注意的是，这种诱导是独立于癌细胞类型的，因为乳腺癌细胞 MDA-MB-231 和胃癌细胞 MKN74 也得到了类似的结果。此外，杂交支架富集具有干细胞特性的侵袭性癌细胞。我们表明，我们的 3D 支架可以触发癌细胞的 EMT，这可以为研究针对转移的抗癌治疗提供有用的模型。
