Co-Culture of Tumor Spheroids and Fibroblasts in a Collagen Matrix-Incorporated Microfluidic Chip Mimics Reciprocal Activation in Solid Tumor Microenvironment

Multicellular 3D culture and interaction with stromal components are considered essential elements in establishing a 'more clinically relevant' tumor model. Matrix-embedded 3D cultures using a microfluidic chip platform can recapitulate the microscale interaction within tumor microenvironm...

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Bibliographic Details
Published in:PloS one 2016-07, Vol.11 (7), p.e0159013-e0159013
Main Authors: Jeong, Su-Yeong, Lee, Ji-Hyun, Shin, Yoojin, Chung, Seok, Kuh, Hyo-Jeong
Format: Article
Language:English
Subjects:
Apoptosis
Biology and Life Sciences
Cancer
Cancer cells
Cell adhesion & migration
Cell culture
Coculture Techniques - instrumentation
Coculture Techniques - methods
Collagen
Collagen - chemistry
Colorectal cancer
Colorectal carcinoma
Colorectal Neoplasms - metabolism
Colorectal Neoplasms - pathology
Development and progression
Drug resistance
Drug screening
Engineering and Technology
Evaluation
Extracellular matrix
Extracellular Matrix - chemistry
Fibroblasts
Fibroblasts - metabolism
Fibroblasts - pathology
Fibronectin
Growth
Health sciences
Humans
Hydrogels
Lab-On-A-Chip Devices
Mechanical engineering
Medical prognosis
Medical research
Medicine and Health Sciences
Metastasis
Methods
Microenvironments
Microfluidics
Paclitaxel
Physiological aspects
Research and Analysis Methods
Solid tumors
Spheroids
Spheroids, Cellular - metabolism
Spheroids, Cellular - pathology
Stem cells
Studies
Three dimensional models
Tissue culture
Tumor Microenvironment
Tumors
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Summary:Multicellular 3D culture and interaction with stromal components are considered essential elements in establishing a 'more clinically relevant' tumor model. Matrix-embedded 3D cultures using a microfluidic chip platform can recapitulate the microscale interaction within tumor microenvironments. As a major component of tumor microenvironment, cancer-associated fibroblasts (CAFs) play a role in cancer progression and drug resistance. Here, we present a microfluidic chip-based tumor tissue culture model that integrates 3D tumor spheroids (TSs) with CAF in proximity within a hydrogel scaffold. HT-29 human colorectal carcinoma cells grew into 3D TSs and the growth was stimulated when co-cultured with fibroblasts as shown by 1.5-folds increase of % changes in diameter over 5 days. TS cultured for 6 days showed a reduced expression of Ki-67 along with increased expression of fibronectin when co-cultured with fibroblasts compared to mono-cultured TSs. Fibroblasts were activated under co-culture conditions, as demonstrated by increases in α-SMA expression and migratory activity. When exposed to paclitaxel, a survival advantage was observed in TSs co-cultured with activated fibroblasts. Overall, we demonstrated the reciprocal interaction between TSs and fibroblasts in our 7-channel microfluidic chip. The co-culture of 3D TS-CAF in a collagen matrix-incorporated microfluidic chip may be useful to study the tumor microenvironment and for evaluation of drug screening and evaluation.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0159013