Three-Dimensional Hepatocellular Carcinoma/Fibroblast Model on a Nanofibrous Membrane Mimics Tumor Cell Phenotypic Changes and Anticancer Drug Resistance

被引:5
|
作者
Binh Duong Le [1 ]
Kang, Donggu [2 ]
Yun, Seokhwan [3 ]
Jeong, Young Hun [4 ]
Kwak, Jong-Young [5 ]
Yoon, Sik [6 ]
Jin, Songwan [3 ]
机构
[1] Korea Polytech Univ, Dept Adv Convergence Technol, Siheung Si 15073, Gyoenggi Do, South Korea
[2] Korea Polytech Univ, Dept Mech Syst Engn, Siheung Si 15073, Gyoenggi Do, South Korea
[3] Korea Polytech Univ, Dept Mech Engn, Siheung Si 15073, Gyoenggi Do, South Korea
[4] Kyungpook Natl Univ, Sch Mech Engn, Daegu 702701, South Korea
[5] Ajou Univ, Sch Med, Dept Pharmacol, Suwon 442721, South Korea
[6] Pusan Natl Univ, Dept Anat, Sch Med, Yangsan 626770, South Korea
基金
新加坡国家研究基金会;
关键词
tumor microenvironment; hepatocellular carcinoma; nanofibrous membrane; EPITHELIAL-MESENCHYMAL TRANSITION; FAMILY PROTEINS; 3D CULTURE; CANCER; PLASTICITY; MATRIX;
D O I
10.3390/nano8020064
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Three-dimensional (3D) in vitro tissue or organ models can effectively mimic the complex microenvironment of many types of human tissues for medical applications. Unfortunately, development of 3D cancer models, which involve cancer/stromal cells in a 3D environment, has remained elusive due to the extreme complexity of the tumor microenvironment (TME) and the stepwise progression of human cancer. Here, we developed hepatocellular carcinoma (HCC) models, which consist of fibroblasts as stromal cells, HCC cells, and a nanofibrous membrane to mimic the complex TME. The 3D HCC models were fabricated using three distinct culture methods: cancer cells grown directly on the nanofibrous membrane (mono model), fibroblasts covering the nanofibrous membrane (layer model), and both cancer cells and fibroblasts grown on the nanofibrous membrane (mixed model). Interestingly, the mono model and layer model showed similar tissue structures, whereas the mixed model resulted in phenotypic changes to the cancer cells. Further analysis demonstrated that the mixed models promoted the expression of fibronectin and vimentin, and showed higher resistance to anticancer drugs compared with the other models. Thus, our 3D HCC model could be utilized for testing efficient anticancer therapies at various stages of cancer, with potential application to different tumor types.
引用
收藏
页数:11
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