Functional investigation of NCI-H460-inducible myofibroblasts on the chemoresistance to VP-16 with a microfluidic 3D co-culture device.

Fibroblasts, the major cell type in tumor stroma, are essential for tumor growth and survival, and represent an important therapeutic target for cancers. Here we presented a microfluidic co-culture device in which the three-dimensional (3D) matrix was employed to reconstruct an in vivo-like fibrobla...

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Main Authors: Yuanyuan Hao, Lichuan Zhang, Jiarui He, Zhe Guo, Li Ying, Zhiyun Xu, Jianing Zhang, Jianxin Lu, Qi Wang
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2013-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3629031?pdf=render
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author Yuanyuan Hao
Lichuan Zhang
Jiarui He
Zhe Guo
Li Ying
Zhiyun Xu
Jianing Zhang
Jianxin Lu
Qi Wang
author_facet Yuanyuan Hao
Lichuan Zhang
Jiarui He
Zhe Guo
Li Ying
Zhiyun Xu
Jianing Zhang
Jianxin Lu
Qi Wang
author_sort Yuanyuan Hao
collection DOAJ
description Fibroblasts, the major cell type in tumor stroma, are essential for tumor growth and survival, and represent an important therapeutic target for cancers. Here we presented a microfluidic co-culture device in which the three-dimensional (3D) matrix was employed to reconstruct an in vivo-like fibroblast-tumor cell microenvironment for investigation of the role of myofibroblasts induced by lung cancer cells in the chemoresistance to VP-16. Composed of a double-layer chip and an injection pump, the device houses fibroblasts and lung cancer cells co-cultured in 3D matrix and 2D mode to induce fibroblasts to become myofibroblasts with the supplement of the medium continuously. With this device, we verified that the cytokines secreted by lung cancer cells could effectively transform the fibroblasts into myofibroblasts. Moreover, compared to fibroblasts, the myofibroblasts showed higher resistance to anticancer drug VP-16. We also demonstrated that this kind of acquired resistance in myofibroblasts was associated with the expression of Glucose-regulated protein 78 (GP78). We concluded that this device allows for the assay to characterize various cellular events in a single device sequentially, facilitating a better understanding of the interactions among heterotypic cells in a sophisticated microenvironment.
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spelling doaj.art-6dda9eaa95bc49fc9d78db1e334a27342022-12-21T22:53:13ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0184e6175410.1371/journal.pone.0061754Functional investigation of NCI-H460-inducible myofibroblasts on the chemoresistance to VP-16 with a microfluidic 3D co-culture device.Yuanyuan HaoLichuan ZhangJiarui HeZhe GuoLi YingZhiyun XuJianing ZhangJianxin LuQi WangFibroblasts, the major cell type in tumor stroma, are essential for tumor growth and survival, and represent an important therapeutic target for cancers. Here we presented a microfluidic co-culture device in which the three-dimensional (3D) matrix was employed to reconstruct an in vivo-like fibroblast-tumor cell microenvironment for investigation of the role of myofibroblasts induced by lung cancer cells in the chemoresistance to VP-16. Composed of a double-layer chip and an injection pump, the device houses fibroblasts and lung cancer cells co-cultured in 3D matrix and 2D mode to induce fibroblasts to become myofibroblasts with the supplement of the medium continuously. With this device, we verified that the cytokines secreted by lung cancer cells could effectively transform the fibroblasts into myofibroblasts. Moreover, compared to fibroblasts, the myofibroblasts showed higher resistance to anticancer drug VP-16. We also demonstrated that this kind of acquired resistance in myofibroblasts was associated with the expression of Glucose-regulated protein 78 (GP78). We concluded that this device allows for the assay to characterize various cellular events in a single device sequentially, facilitating a better understanding of the interactions among heterotypic cells in a sophisticated microenvironment.http://europepmc.org/articles/PMC3629031?pdf=render
spellingShingle Yuanyuan Hao
Lichuan Zhang
Jiarui He
Zhe Guo
Li Ying
Zhiyun Xu
Jianing Zhang
Jianxin Lu
Qi Wang
Functional investigation of NCI-H460-inducible myofibroblasts on the chemoresistance to VP-16 with a microfluidic 3D co-culture device.
PLoS ONE
title Functional investigation of NCI-H460-inducible myofibroblasts on the chemoresistance to VP-16 with a microfluidic 3D co-culture device.
title_full Functional investigation of NCI-H460-inducible myofibroblasts on the chemoresistance to VP-16 with a microfluidic 3D co-culture device.
title_fullStr Functional investigation of NCI-H460-inducible myofibroblasts on the chemoresistance to VP-16 with a microfluidic 3D co-culture device.
title_full_unstemmed Functional investigation of NCI-H460-inducible myofibroblasts on the chemoresistance to VP-16 with a microfluidic 3D co-culture device.
title_short Functional investigation of NCI-H460-inducible myofibroblasts on the chemoresistance to VP-16 with a microfluidic 3D co-culture device.
title_sort functional investigation of nci h460 inducible myofibroblasts on the chemoresistance to vp 16 with a microfluidic 3d co culture device
url http://europepmc.org/articles/PMC3629031?pdf=render
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