An omentum-inspired 3D PEG hydrogel for identifying ECM-drivers of drug resistant ovarian cancer
An omentum-inspired 3D PEG hydrogel for identifying ECM-drivers of drug resistant ovarian cancer
复制标题
DOI：
10.1063/1.5091713
复制
发表时间：
2019-06-01
影响因子：
6
通讯作者：
Peyton, Shelly R.
中科院分区：
文献类型：
--
作者：
Brooks, Elizabeth A.;Gencoglu, Maria F.;Peyton, Shelly R.
卵巢癌（OvCa）是一种具有挑战性的疾病，治疗由于不良的筛查技术和晚期诊断。由于70%的病例患者会复发，因此迫切需要额外的治疗方案。临床治疗选择的有限性可能是在标准组织培养聚苯乙烯（TCPS）的早期药物筛选中预测不佳的结果。TCPS不能捕捉到细胞在体内经历的机械和生化线索，而这些线索会影响细胞对药物的反应。因此，一个能够捕捉细胞在体内经历的一些微环境特征的体外模型可以更好地了解药物反应。在这项研究中，我们在微孔中形成了三维多细胞肿瘤球体（MCTS），并将它们包裹在三维网膜激发的水凝胶中。与TCPS的单层水凝胶相比，SKOV-3 MCTS在我们的3D水凝胶中对紫杉醇具有抗性。在临床应用方面，我们测试了接受紫杉醇治疗的卵巢癌腹水球（OCAS）患者的细胞，使用3D网膜激发水凝胶预测的药物反应表明，这些样本缺乏紫杉醇反应。此外，我们观察到胶原蛋白在包裹的SKOV-3 MCTS周围产生，但在TCPS上不明显。我们的研究结果表明，我们的3D网膜启发水凝胶是一种改进的体外药物测试平台，可以研究OvCa对患者来源细胞的药物反应，并帮助我们确定胶原蛋白3是三维紫杉醇耐药的潜在驱动因素。(C) 2019作者。除另有说明外，所有文章内容均遵循知识共享署名（CC BY）许可协议（http://creativecommons.org/licenses/by/4.0/）。
Ovarian cancer (OvCa) is a challenging disease to treat due to poor screening techniques and late diagnosis. There is an urgent need for additional therapy options, as patients recur in 70% of cases. The limited availability of clinical treatment options could be a result of poor predictions in early stage drug screens on standard tissue culture polystyrene (TCPS). TCPS does not capture the mechanical and biochemical cues that cells experience in vivo, which can impact how cells will respond to a drug. Therefore, an in vitro model that captures some of the microenvironment features that the cells experience in vivo could provide better insights into drug responses. In this study, we formed 3D multicellular tumor spheroids (MCTS) in microwells and encapsulated them in 3D omentum-inspired hydrogels. SKOV-3 MCTS were resistant to Paclitaxel in our 3D hydrogels compared to a monolayer on TCPS. Toward clinical application, we tested cells from patients [ovarian carcinoma ascites spheroids (OCAS)] who had been treated with Paclitaxel, and drug responses predicted by using the 3D omentum-inspired hydrogels demonstrated the lack of the Paclitaxel response of these samples. Additionally, we observed the presence of collagen production around the encapsulated SKOV-3 MCTS, but not significantly on TCPS. Our results demonstrated that our 3D omentum-inspired hydrogel is an improved in vitro drug testing platform to study the OvCa drug response for patient-derived cells and helped us identify collagen 3 as a potential driver of Paclitaxel resistance in 3D. (C) 2019 Author(s). All article content, except where otherwise noted, is licensed under a Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).