3D culture enhances chemoresistance of ALL Jurkat cell line by increasing DDR1 expression

Guo,Jun; Zhao,Chunting; Yao,Ruyong; Sui,Aihua; Sun,Lingjie; Liu,Xiaodan; Wu,Shaoling; Su,Zhan; Li,Tianlan; Liu,Shanshan; Gao,Yan; Liu,Jiaxiu; Feng,Xianqi; Wang,Wei; Zhao,Hongguo; Cui,Zhongguang; Li,Guanglun; Meng,Fanjun

doi:10.3892/etm.2019.7153

3D culture enhances chemoresistance of ALL Jurkat cell line by increasing DDR1 expression

Authors:
- Jun Guo
- Chunting Zhao
- Ruyong Yao
- Aihua Sui
- Lingjie Sun
- Xiaodan Liu
- Shaoling Wu
- Zhan Su
- Tianlan Li
- Shanshan Liu
- Yan Gao
- Jiaxiu Liu
- Xianqi Feng
- Wei Wang
- Hongguo Zhao
- Zhongguang Cui
- Guanglun Li
- Fanjun Meng
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Affiliations: College of Medicine, Qingdao University, Qingdao, Shandong 266071, P.R. China, Department of Hematology, Affiliated Hospital of Qingdao University, Qingdao, Shandong 266555, P.R. China, Central Laboratory, Affiliated Hospital of Medical College, Qingdao University, Qingdao, Shandong 266035, P.R. China
Published online on: January 4, 2019 https://doi.org/10.3892/etm.2019.7153
Pages: 1593-1600
Copyright: © Guo et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Three dimensional (3D) culture has gradually become a research hotspot in the field of drug screening, stem cell research, and tissue engineering due to its more physiological-like morphology and function. In this study, we compared the differences of cell proliferation, population, protein expression and chemoresistance profiles between two dimensional (2D) and 3D culture of acute lymphoblastic leukemia (ALL) Jurkat cell line. Polycaprolactone (PCL) is used for 3D culture owing to its biochemical properties and compatibility. Culturing of ALL Jurkat cell line in collagen type Ⅰ coated polycaprolactone scaffold for 168 h increased cell proliferation, attachment, as well as the drug resistance to cytarabine (Ara-C) and daunorubicin (DNR) without changing the original CD2+CD3+CD4+dimCD8-CD34-CD45+dim phenotype, compared to uncoated PCL scaffold and tissue culture plate systems. Molecularly, increased chemoresistance is associated with the upregulation of discoidin domain receptor 1 (DDR1) and transcription factor STAT3. Inhibition of DDR1 activity by DDR1-specific inhibitor DDR-IN-1 accelerated cell death in the presence of Ara-C, DNR or their combination. These results demonstrated that 3D culture enhances chemoresistance of ALL Jurkat cell line by increasing DDR1 expression. Importantly, the cell adhesion-mediated drug resistance induced by DDR1 in the scaffold was similar to the clinical situation, indicating the 3D culture of cancer cells recapitulate the in vivo tumor environment and this platform can be used as a promising pre-clinic drug-screen system.

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