Department of Thoracic Surgery, Tumor Hospital of Shaanxi Province, Affiliated to the Medical College of Xi'an Jiaotong University, Xi'an 710061, Shaanxi, China.
Department of Pathology, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an 710061, Shaanxi, China.
Acta Biomater. 2018 Apr 15;71:460-473. doi: 10.1016/j.actbio.2018.03.020. Epub 2018 Mar 17.
Acellular tumor extracellular matrices (ECMs) have limitations when employed as three-dimensional (3D) scaffolds for tumor engineering. In this work, methylene blue-mediated photooxidation was used to crosslink acellular tumor ECMs. Photooxidative crosslinking greatly increased the stiffness of acellular tumor ECM scaffolds but barely altered the Amide III band of the secondary structure of polypeptides and proteins. MCF-7, HepG2 and A549 cells cultured on photooxidatively crosslinked acellular tumor ECM scaffolds exhibited greater cell number per scaffold, more IL-8 and VEGF secretion, and increase migration and invasion abilities than cells cultured on uncrosslinked acellular tumor ECM scaffolds. The three tumor cell lines cultured on the stiffer photooxidatively crosslinked acellular matrices acquire mesenchymal properties (mesenchymal shift) and dedifferentiated phenotypes. Furthermore, the malignant phenotypes induced in vitro when cultured on the crosslinked scaffold promoted the in vivo tumor growth of BALB/c nude mice. Finally, the dedifferentiated cancer cells, including MCF-7, HepG2 and A549 cells, were less sensitive to chemotherapeutics. Thus, photooxidatively crosslinked acellular tumor ECMs have potentials as 3D tumor engineering scaffolds for cancer research.
Natural material scaffolds have been successfully used as 3D matrices to study the in vitro tumor cell growth and mimic the in vivo tumor microenvironment. Acellular tumor ECMs are developed as 3D scaffolds for tumor engineering but have limitations in terms of elastic modulus and cell spheroid formation. Here we use methylene blue-mediated photooxidation to crosslink acellular tumor ECMs and investigate the influence of photooxidative crosslinking on structural, mechanical and biological characteristics of acellular tumor ECM scaffolds. It is the first study to evaluate the feasibility of photooxidatively crosslinked acellular tumor ECMs as 3D scaffolds for cancer research and the results are encouraging. Moreover, this study provides new research areas in regard to photodynamic therapy (PDT) for Cancer.
无细胞肿瘤细胞外基质 (ECM) 在作为肿瘤工程的三维 (3D) 支架使用时存在局限性。在这项工作中，使用亚甲蓝介导的光氧化来交联无细胞肿瘤 ECM。光氧化交联大大增加了无细胞肿瘤 ECM 支架的刚性，但几乎没有改变多肽和蛋白质二级结构的酰胺 III 带。与培养在未交联的无细胞肿瘤 ECM 支架上的细胞相比，在光氧化交联的无细胞肿瘤 ECM 支架上培养的 MCF-7、HepG2 和 A549 细胞每支架的细胞数量更多，分泌的 IL-8 和 VEGF 更多，迁移和侵袭能力也更强。在更硬的光氧化交联无细胞基质上培养的三种肿瘤细胞系获得间充质特性（间质转移）和去分化表型。此外，在交联支架上培养时诱导的体外恶性表型促进了 BALB/c 裸鼠体内肿瘤的生长。最后，包括 MCF-7、HepG2 和 A549 细胞在内的去分化癌细胞对化疗药物的敏感性降低。因此，光氧化交联的无细胞肿瘤 ECM 具有作为癌症研究 3D 肿瘤工程支架的潜力。
天然材料支架已成功用作体外研究肿瘤细胞生长的 3D 基质，并模拟体内肿瘤微环境。无细胞肿瘤 ECM 被开发为肿瘤工程的 3D 支架，但在弹性模量和细胞球体形成方面存在局限性。在这里，我们使用亚甲蓝介导的光氧化来交联无细胞肿瘤 ECM，并研究光氧化交联对无细胞肿瘤 ECM 支架的结构、力学和生物学特性的影响。这是第一项评估光氧化交联的无细胞肿瘤 ECM 作为癌症研究 3D 支架的可行性的研究，结果令人鼓舞。此外，这项研究为光动力疗法 (PDT) 治疗癌症提供了新的研究领域。
