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Three-Dimensional Hepatocellular Carcinoma/Fibroblast Model on a Nanofibrous Membrane Mimics Tumor Cell Phenotypic Changes and Anticancer Drug Resistance
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 e...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5852456/ https://www.ncbi.nlm.nih.gov/pubmed/29370123 http://dx.doi.org/10.3390/nano8020064 |
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author | Le, Binh Duong Kang, Donggu Yun, Seokhwan Jeong, Young Hun Kwak, Jong-Young Yoon, Sik Jin, Songwan |
author_facet | Le, Binh Duong Kang, Donggu Yun, Seokhwan Jeong, Young Hun Kwak, Jong-Young Yoon, Sik Jin, Songwan |
author_sort | Le, Binh Duong |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-5852456 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-58524562018-03-16 Three-Dimensional Hepatocellular Carcinoma/Fibroblast Model on a Nanofibrous Membrane Mimics Tumor Cell Phenotypic Changes and Anticancer Drug Resistance Le, Binh Duong Kang, Donggu Yun, Seokhwan Jeong, Young Hun Kwak, Jong-Young Yoon, Sik Jin, Songwan Nanomaterials (Basel) Article 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. MDPI 2018-01-25 /pmc/articles/PMC5852456/ /pubmed/29370123 http://dx.doi.org/10.3390/nano8020064 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Le, Binh Duong Kang, Donggu Yun, Seokhwan Jeong, Young Hun Kwak, Jong-Young Yoon, Sik Jin, Songwan Three-Dimensional Hepatocellular Carcinoma/Fibroblast Model on a Nanofibrous Membrane Mimics Tumor Cell Phenotypic Changes and Anticancer Drug Resistance |
title | Three-Dimensional Hepatocellular Carcinoma/Fibroblast Model on a Nanofibrous Membrane Mimics Tumor Cell Phenotypic Changes and Anticancer Drug Resistance |
title_full | Three-Dimensional Hepatocellular Carcinoma/Fibroblast Model on a Nanofibrous Membrane Mimics Tumor Cell Phenotypic Changes and Anticancer Drug Resistance |
title_fullStr | Three-Dimensional Hepatocellular Carcinoma/Fibroblast Model on a Nanofibrous Membrane Mimics Tumor Cell Phenotypic Changes and Anticancer Drug Resistance |
title_full_unstemmed | Three-Dimensional Hepatocellular Carcinoma/Fibroblast Model on a Nanofibrous Membrane Mimics Tumor Cell Phenotypic Changes and Anticancer Drug Resistance |
title_short | Three-Dimensional Hepatocellular Carcinoma/Fibroblast Model on a Nanofibrous Membrane Mimics Tumor Cell Phenotypic Changes and Anticancer Drug Resistance |
title_sort | three-dimensional hepatocellular carcinoma/fibroblast model on a nanofibrous membrane mimics tumor cell phenotypic changes and anticancer drug resistance |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5852456/ https://www.ncbi.nlm.nih.gov/pubmed/29370123 http://dx.doi.org/10.3390/nano8020064 |
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