Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Le, Binh Duong, Kang, Donggu, Yun, Seokhwan, Jeong, Young Hun, Kwak, Jong-Young, Yoon, Sik, Jin, Songwan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
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
_version_ 1783306576236380160
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
work_keys_str_mv AT lebinhduong threedimensionalhepatocellularcarcinomafibroblastmodelonananofibrousmembranemimicstumorcellphenotypicchangesandanticancerdrugresistance
AT kangdonggu threedimensionalhepatocellularcarcinomafibroblastmodelonananofibrousmembranemimicstumorcellphenotypicchangesandanticancerdrugresistance
AT yunseokhwan threedimensionalhepatocellularcarcinomafibroblastmodelonananofibrousmembranemimicstumorcellphenotypicchangesandanticancerdrugresistance
AT jeongyounghun threedimensionalhepatocellularcarcinomafibroblastmodelonananofibrousmembranemimicstumorcellphenotypicchangesandanticancerdrugresistance
AT kwakjongyoung threedimensionalhepatocellularcarcinomafibroblastmodelonananofibrousmembranemimicstumorcellphenotypicchangesandanticancerdrugresistance
AT yoonsik threedimensionalhepatocellularcarcinomafibroblastmodelonananofibrousmembranemimicstumorcellphenotypicchangesandanticancerdrugresistance
AT jinsongwan threedimensionalhepatocellularcarcinomafibroblastmodelonananofibrousmembranemimicstumorcellphenotypicchangesandanticancerdrugresistance