Mechanomimetic 3D Scaffolds as a Humanized In Vitro Model for Ovarian Cancer.
Mechanomimetic 3D Scaffolds as a Humanized In Vitro Model for Ovarian Cancer.
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DOI：
10.3390/cells11050824
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发表时间：
2022-02-26
期刊：
影响因子：
6
通讯作者：
Taraballi F
中科院分区：
文献类型：
--
作者：
Paradiso F;Lenna S;Gazze SA;Garcia Parra J;Murphy K;Margarit L;Gonzalez D;Francis L;Taraballi F
组织的机械稳态可以响应于创伤或疾病（例如癌症）而改变，从而导致改变的机械转导途径，其已显示影响肿瘤发展、进展和治疗方法的功效。具体而言，卵巢癌进展与组织硬度和纤维化的增加平行。由于体内模型难以研究，将组织力学与改变的细胞和分子特性联系起来需要能够模拟正常和肿瘤力学特征的先进的、可调的体外3D模型。首先，我们表征了正常人卵巢和高级别浆液性（HGSC）卵巢癌组织硬度，以分别精确地模拟它们在基于I型胶原的海绵支架上的机械特征，软（NS）和硬（MS）。我们利用三种卵巢癌细胞系（OVCAR-3，Caov-3和SKOV 3）来评估活力，形态，增殖和对阿霉素和脂质体阿霉素治疗的敏感性在不同的机械微环境下的变化。高硬度的基质促进Caov-3和SKOV 3细胞的增殖而不改变其形态，并且仅在SKOV 3细胞中上调力学传感器雅普/TAZ。培养7天后，OVCAR 3和SKOV 3均降低了MS支架储能模量（刚度），表明细胞增殖和基质软化之间存在联系。最后，高基质硬度导致响应于多柔比星的较高OVCAR-3和SKOV 3细胞毒性。这项研究表明，仿生多孔支架的承诺，有效地纳入三维癌症建模的机械参数。此外，这项工作建立了使用多孔支架研究卵巢癌细胞对微环境中机械变化的反应，并作为一个有意义的平台来研究化疗耐药性和药物反应。
The mechanical homeostasis of tissues can be altered in response to trauma or disease, such as cancer, resulting in altered mechanotransduction pathways that have been shown to impact tumor development, progression, and the efficacy of therapeutic approaches. Specifically, ovarian cancer progression is parallel to an increase in tissue stiffness and fibrosis. With in vivo models proving difficult to study, tying tissue mechanics to altered cellular and molecular properties necessitate advanced, tunable, in vitro 3D models able to mimic normal and tumor mechanic features. First, we characterized normal human ovary and high-grade serous (HGSC) ovarian cancer tissue stiffness to precisely mimic their mechanical features on collagen I-based sponge scaffolds, soft (NS) and stiff (MS), respectively. We utilized three ovarian cancer cell lines (OVCAR-3, Caov-3, and SKOV3) to evaluate changes in viability, morphology, proliferation, and sensitivity to doxorubicin and liposomal doxorubicin treatment in response to a mechanically different microenvironment. High substrate stiffness promoted the proliferation of Caov-3 and SKOV3 cells without changing their morphology, and upregulated mechanosensors YAP/TAZ only in SKOV3 cells. After 7 days in culture, both OVCAR3 and SKOV3 decreased the MS scaffold storage modulus (stiffness), suggesting a link between cell proliferation and the softening of the matrix. Finally, high matrix stiffness resulted in higher OVCAR-3 and SKOV3 cell cytotoxicity in response to doxorubicin. This study demonstrates the promise of biomimetic porous scaffolds for effective inclusion of mechanical parameters in 3D cancer modeling. Furthermore, this work establishes the use of porous scaffolds for studying ovarian cancer cells response to mechanical changes in the microenvironment and as a meaningful platform from which to investigate chemoresistance and drug response.
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3D多孔壳聚糖 - 甲酸盐支架促进癌症干细胞的增殖和富集。
DOI：
10.1039/c6tb01713d
发表时间：
2016-10-14
期刊：
Journal of materials chemistry. B
影响因子：
--
作者：
Florczyk SJ;Kievit FM;Wang K;Erickson AE;Ellenbogen RG;Zhang M
通讯作者：
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影响因子：
16.6
作者：
Domcke, Silvia;Sinha, Rileen;Levine, Douglas A.;Sander, Chris;Schultz, Nikolaus
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Schultz, Nikolaus
DOI：
10.1039/c5ib00040h
发表时间：
2015-10
期刊：
Integrative biology : quantitative biosciences from nano to macro
影响因子：
--
作者：
Acerbi I;Cassereau L;Dean I;Shi Q;Au A;Park C;Chen YY;Liphardt J;Hwang ES;Weaver VM
通讯作者：
Weaver VM
影响因子：
3.7
作者：
Beaufort CM;Helmijr JC;Piskorz AM;Hoogstraat M;Ruigrok-Ritstier K;Besselink N;Murtaza M;van IJcken WF;Heine AA;Smid M;Koudijs MJ;Brenton JD;Berns EM;Helleman J
通讯作者：
Helleman J
影响因子：
82.9
作者：
Binnewies M;Roberts EW;Kersten K;Chan V;Fearon DF;Merad M;Coussens LM;Gabrilovich DI;Ostrand-Rosenberg S;Hedrick CC;Vonderheide RH;Pittet MJ;Jain RK;Zou W;Howcroft TK;Woodhouse EC;Weinberg RA;Krummel MF
通讯作者：
Krummel MF