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用于体外肿瘤模型的丝素蛋白 3D 基质的构建

Engineered silk fibroin protein 3D matrices for in vitro tumor model.

机构信息

Department of Biotechnology, Indian Institute of Technology, Kharagpur 721302, India.

出版信息

Biomaterials. 2011 Mar;32(8):2149-59. doi: 10.1016/j.biomaterials.2010.11.052. Epub 2010 Dec 16.

Abstract

3D in vitro model systems that are able to mimic the in vivo microenvironment are now highly sought after in cancer research. Antheraea mylitta silk fibroin protein matrices were investigated as potential biomaterial for in vitro tumor modeling. We compared the characteristics of MDA-MB-231 cells on A. mylitta, Bombyx mori silk matrices, Matrigel, and tissue culture plates. The attachment and morphology of the MDA-MB-231 cell line on A. mylitta silk matrices was found to be better than on B. mori matrices and comparable to Matrigel and tissue culture plates. The cells grown in all 3D cultures showed more MMP-9 activity, indicating a more invasive potential. In comparison to B. mori fibroin, A. mylitta fibroin not only provided better cell adhesion, but also improved cell viability and proliferation. Yield coefficient of glucose consumed to lactate produced by cells on 3D A. mylitta fibroin was found to be similar to that of cancer cells in vivo. LNCaP prostate cancer cells were also cultured on 3D A. mylitta fibroin and they grew as clumps in long term culture. The results indicate that A. mylitta fibroin scaffold can provide an easily manipulated microenvironment system to investigate individual factors such as growth factors and signaling peptides, as well as evaluation of anticancer drugs.

摘要

目前,癌症研究领域迫切需要能够模拟体内微环境的 3D 体外模型系统。本研究旨在探讨野桑蚕(Antheraea mylitta)丝素蛋白基质是否可作为体外肿瘤建模的潜在生物材料。我们将 MDA-MB-231 细胞在野桑蚕丝素蛋白基质、家蚕丝素蛋白基质、Matrigel 基质和细胞培养板上的特性进行了比较。结果表明,与 B. mori 丝素蛋白基质相比,MDA-MB-231 细胞在野桑蚕丝素蛋白基质上的黏附性和形态更好,与 Matrigel 和细胞培养板相当。在所有 3D 培养物中生长的细胞 MMP-9 活性更高,表明其侵袭潜能更强。与 B. mori 丝素蛋白相比,A. mylitta 丝素蛋白不仅提供了更好的细胞黏附性,而且提高了细胞活力和增殖能力。我们还发现,3D A. mylitta 丝素蛋白上细胞消耗葡萄糖产生的乳酸产量与体内癌细胞的产率系数相似。LNCaP 前列腺癌细胞也在 3D A. mylitta 丝素蛋白上培养,它们在长期培养中会形成团块。结果表明,A. mylitta 丝素蛋白支架可为研究生长因子和信号肽等单个因素以及评估抗癌药物提供一个易于操作的微环境系统。

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