title: Co-Culture of Tumor Spheroids and Fibroblasts in a Collagen Matrix-Incorporated Microfluidic Chip Mimics Reciprocal Activation in Solid Tumor Microenvironment.
abstract: 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.
authors.affiliation: Department of Biomedicine & Health Sciences, Graduate School, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Su-Yeong
authors.initials: SY
authors.lastname: Jeong
authors.affiliation: Department of Biomedicine & Health Sciences, Graduate School, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Ji-Hyun
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America.
authors.forename: Yoojin
authors.initials: Y
authors.lastname: Shin
authors.affiliation: School of Mechanical Engineering, Korea University, Seoul, Republic of Korea.
authors.forename: Seok
authors.initials: S
authors.lastname: Chung
authors.affiliation: Department of Biomedicine & Health Sciences, Graduate School, The Catholic University of Korea, Seoul, Republic of Korea.|Cancer Evolution Research Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.|Department of Medical Life Sciences, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Hyo-Jeong
authors.initials: HJ
authors.lastname: Kuh
mesh_terms: D018920:Coculture Techniques / Q000295:instrumentation / Q000379:methods; D003094:Collagen / Q000737:chemistry*; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D005109:Extracellular Matrix / Q000737:chemistry; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D056656:Lab-On-A-Chip Devices; D018874:Spheroids, Cellular / Q000378:metabolism* / Q000473:pathology; D059016:Tumor Microenvironment
chemical_list: D003094:Collagen