Peptide-protein coassembling matrices as a biomimetic 3D model of ovarian cancer.

Peptide-protein coassembling matrices as a biomimetic 3D model of ovarian cancer.
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DOI:
10.1126/sciadv.abb3298
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发表时间:
2020-10
期刊:
影响因子:
13.6
通讯作者:
Mata A
Mata A
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Hedegaard CL;Redondo-Gómez C;Tan BY;Ng KW;Loessner D;Mata A

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由自组装肽和细胞外基质蛋白组成的生物工程基质可以模拟肿瘤微环境。生物工程三维(3D)基质扩展了我们的实验库,以生物相关的方式研究肿瘤的生长和进展。在这里,我们使用肽两亲体(PAs)与细胞外基质(ECM)蛋白共同组装和组织,产生可调的肿瘤微环境3D模型。该基质旨在模拟患者肿瘤的物理和生物分子特征。我们纳入了用于人卵巢癌、内皮细胞和间充质干细胞3D培养的特异性表位、PA纳米纤维和ECM大分子。多细胞结构支持肿瘤球体的形成,球体周围有广泛的f -肌动蛋白网络,促进细胞间的通信,并与Matrigel中观察到的细胞-基质相互作用和封装反应进行比较。我们对临床使用的化疗药物进行了概念验证研究,以验证多细胞结构的功能。我们的研究表明,肽蛋白共组装基质可以作为原发性卵巢肿瘤多细胞肿瘤微环境的确定模型。
Bioengineered matrices from self-assembling peptides and extracellular matrix proteins can model the tumor microenvironment. Bioengineered three-dimensional (3D) matrices expand our experimental repertoire to study tumor growth and progression in a biologically relevant, yet controlled, manner. Here, we used peptide amphiphiles (PAs) to coassemble with and organize extracellular matrix (ECM) proteins producing tunable 3D models of the tumor microenvironment. The matrix was designed to mimic physical and biomolecular features of tumors present in patients. We included specific epitopes, PA nanofibers, and ECM macromolecules for the 3D culture of human ovarian cancer, endothelial, and mesenchymal stem cells. The multicellular constructs supported the formation of tumor spheroids with extensive F-actin networks surrounding the spheroids, enabling cell-cell communication, and comparative cell-matrix interactions and encapsulation response to those observed in Matrigel. We conducted a proof-of-concept study with clinically used chemotherapeutics to validate the functionality of the multicellular constructs. Our study demonstrates that peptide-protein coassembling matrices serve as a defined model of the multicellular tumor microenvironment of primary ovarian tumors.
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