Wang Hejing, Qian Junmin, Zhang Yaping, Xu Weijun, Xiao Juxiang, Suo Aili
Department of Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, No. 277, Yanta West Road, Xi'an, Shanxi People's Republic of China.
State Key Laboratory for Mechanical Behaviours of Materials, Xi'an Jiaotong University, Xi'an, 710049 China.
Cancer Cell Int. 2017 May 16;17:55. doi: 10.1186/s12935-017-0424-8. eCollection 2017.
Breast cancer negatively affects women's health worldwide. The tumour microenvironment plays a critical role in tumour initiation, proliferation, and metastasis. Cancer cells are traditionally grown in two-dimensional (2D) cultures as monolayers on a flat solid surface lacking cell-cell and cell-matrix interactions. These experimental conditions deviate from the clinical situation. Improved experimental systems that can mimic the in vivo situation are required to discover new therapies, particularly for anti-angiogenic agents that mainly target intercellular factors and play an essential role in treating some cancers.
Chitosan can be modified to construct three-dimensional (3D) tumour models. Here, we report an in vitro 3D tumour model using a hydroxyethyl chitosan/glycidyl methacrylate (HECS-GMA) hydrogel produced by a series of chitosan modifications. Parameters relating to cell morphology, viability, proliferation, and migration were analysed using breast cancer MCF-7 cells. In a xenograft model, secretion of angiogenesis-related growth factors and the anti-angiogenic efficacy of Endostar and Bevacizumab in cells grown in HECS-GMA hydrogels were assessed by immunohistochemistry.
Hydroxyethyl chitosan/glycidyl methacrylate hydrogels had a highly porous microstructure, mechanical properties, swelling ratio, and morphology consistent with a 3D tumour model. Compared with a 2D monolayer culture, breast cancer MCF-7 cells residing in the HECS-GMA hydrogels grew as tumour-like clusters in a 3D formation. In a xenograft model, MCF-7 cells cultured in the HECS-GMA hydrogels had increased secretion of angiogenesis-related growth factors. Recombinant human endostatin (Endostar), but not Bevacizumab (Avastin), was an effective anti-angiogenic agent in HECS-GMA hydrogels.
The HECS-GMA hydrogel provided a 3D tumour model that mimicked the in vivo cancer microenvironment and supported the growth of MCF7 cells better than traditional tissue culture plates. The HECS-GMA hydrogel may offer an improved platform to minimize the gap between traditional tissue culture plates and clinical applicability. In addition, the anti-angiogenic efficacy of drugs such as Endostar and Bevacizumab can be more comprehensively studied and assessed in HECS-GMA hydrogels.
乳腺癌对全球女性健康产生负面影响。肿瘤微环境在肿瘤的起始、增殖和转移中起着关键作用。传统上，癌细胞在二维（2D）培养中以单层形式生长在缺乏细胞 - 细胞和细胞 - 基质相互作用的平坦固体表面上。这些实验条件与临床情况不符。需要改进的实验系统来模拟体内情况，以发现新的治疗方法，特别是对于主要靶向细胞间因子并在治疗某些癌症中起重要作用的抗血管生成药物。
壳聚糖可以被修饰以构建三维（3D）肿瘤模型。在此，我们报告一种使用通过一系列壳聚糖修饰产生的羟乙基壳聚糖/甲基丙烯酸缩水甘油酯（HECS - GMA）水凝胶的体外3D肿瘤模型。使用乳腺癌MCF - 7细胞分析与细胞形态、活力、增殖和迁移相关的参数。在异种移植模型中，通过免疫组织化学评估血管生成相关生长因子的分泌以及恩度和贝伐单抗在HECS - GMA水凝胶中生长的细胞中的抗血管生成功效。
羟乙基壳聚糖/甲基丙烯酸缩水甘油酯水凝胶具有高度多孔的微观结构、机械性能、溶胀率和与3D肿瘤模型一致的形态。与2D单层培养相比，驻留在HECS - GMA水凝胶中的乳腺癌MCF - 7细胞以3D形式生长为肿瘤样簇。在异种移植模型中，在HECS - GMA水凝胶中培养的MCF - 7细胞增加了血管生成相关生长因子的分泌。重组人内皮抑素（恩度）而非贝伐单抗（阿瓦斯汀）是HECS - GMA水凝胶中的有效抗血管生成药物。
HECS - GMA水凝胶提供了一种3D肿瘤模型，该模型模拟了体内癌症微环境，并且比传统组织培养板更好地支持MCF7细胞的生长。HECS - GMA水凝胶可能提供一个改进的平台，以最小化传统组织培养板与临床适用性之间的差距。此外，恩度和贝伐单抗等药物的抗血管生成功效可以在HECS - GMA水凝胶中得到更全面的研究和评估。
