The enhancement of cancer stem cell properties of MCF-7 cells in 3D collagen scaffolds for modeling of cancer and anti-cancer drugs

被引:242
作者
Chen, Lei [1 ,2 ]
Xiao, Zhifeng [1 ]
Meng, Yue [1 ]
Zhao, Yannan [1 ]
Han, Jin [1 ]
Su, Guannan [1 ,2 ]
Chen, Bing [1 ]
Dai, Jianwu [1 ]
机构
[1] Chinese Acad Sci, Inst Genet & Dev Biol, State Key Lab Mol Dev Biol, Beijing 100190, Peoples R China
[2] Chinese Acad Sci, Grad Sch, Beijing 100190, Peoples R China
关键词
Three-dimensional culture; Breast cancer stem cells; EMT; Collagen scaffolds; MCF-7; E-CADHERIN EXPRESSION; BREAST-CANCER; MESENCHYMAL TRANSITION; CULTURE; CARCINOMA; MATRIX; INVASION; HYPOXIA; RESISTANCE; GROWTH;
D O I
10.1016/j.biomaterials.2011.10.056
中图分类号
R318 [生物医学工程];
学科分类号
100103 [病原生物学];
摘要
Three-dimensional (3D) culture could partially simulate in vivo conditions. In this work, we developed a 3D collagen scaffold to investigate cellular properties of MCF-7 cells. The porous scaffolds not only induced the diversification of cell morphologies but also extended cell proliferation. The expression of pro-angiogenic growth factors and the transcriptions of matrix metalloproteinases (MMPs) were significantly increased in cells cultured in 3D collagen scaffolds. In addition, 3D collagen scaffolds could generate a cell population with the properties of cancer stem cells (CSCs). The upregulation of EMT markers and the downregulation of the epithelial cell marker were observed in cells cultured in collagen scaffolds. The expression of stem cell markers, including OCT4A and SOX2, and breast cancer stem cell signatures, including SOX4, JAG1 and CD49F, was significantly unregulated in 3D collagen scaffolds. The proportion of cells with CSC-like CD44(+)/CD24(-/low) phenotype was notably increased. High-level expression of CSC-associated properties of MCF-7 cells cultured in 3D was further confirmed by high tumorigenicity in vivo. Moreover, xenografts with 3D cells formed larger tumors. The properties of MCF-7 cells in 3D may have partially simulated their in vivo behaviors. Thus, 3D collagen scaffolds might provide a useful platform for anti-cancer therapeutics and CSC research. (C) 2011 Elsevier Ltd. All rights reserved.
引用
收藏
页码:1437 / 1444
页数:8
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