Biological gel-based microchamber array for tumor cell proliferation and migration studies in well-controlled biochemical gradients

作者全名："Yao, Jingru; Li, Guoqiang; Jiao, Yang; Zheng, Yu; Liu, Yanping; Wang, Gao; Zhou, Lianjie; Zhang, Hongfei; Zhang, Xianquan; Shuai, Jianwei; Fan, Qihui; Ye, Fangfu; Lou, Silong; Chen, Guo; Song, Kena; Liao, Yong; Liu, Liyu"

作者地址："[Yao, Jingru; Li, Guoqiang; Liu, Yanping; Wang, Gao; Zhou, Lianjie; Chen, Guo; Song, Kena; Liu, Liyu] Chongqing Univ, Coll Phys, Chongqing Key Lab Soft Condensed Matter Phys & Sm, Chongqing 401331, Peoples R China; [Jiao, Yang; Zheng, Yu] Arizona State Univ, Mat Sci & Engn, Tempe, AZ 85281 USA; [Zhang, Hongfei; Zhang, Xianquan] Hygeia Int Canc Hosp, Chongqing 401331, Peoples R China; [Shuai, Jianwei] Xiamen Univ, Dept Phys, Xiamen 361005, Peoples R China; [Fan, Qihui; Ye, Fangfu] Univ Chinese Acad Sci, Wenzhou Inst, Wenzhou 325000, Peoples R China; [Ye, Fangfu] Chinese Acad Sci, Inst Phys, Beijing Natl Lab Condensed Matter Phys, Beijing 100190, Peoples R China; [Lou, Silong] Chongqing Univ, Canc Hosp, Chongqing 400044, Peoples R China; [Song, Kena] Henan Univ Sci & Technol, Coll Med Technol & Engn, Luoyang 471023, Henan, Peoples R China; [Liao, Yong] Chongqing Med Univ, Affiliated Hosp 2, Inst Viral Hepatitis, Dept Infect Dis, Chongqing 400331, Peoples R China"

通信作者："Song, KN; Liu, LY (corresponding author), Chongqing Univ, Coll Phys, Chongqing Key Lab Soft Condensed Matter Phys & Sm, Chongqing 401331, Peoples R China.; Song, KN (corresponding author), Henan Univ Sci & Technol, Coll Med Technol & Engn, Luoyang 471023, Henan, Peoples R China.; Liao, Y (corresponding author), Chongqing Med Univ, Affiliated Hosp 2, Inst Viral Hepatitis, Dept Infect Dis, Chongqing 400331, Peoples R China."

来源：LAB ON A CHIP

ESI学科分类：CHEMISTRY

WOS号：WOS:000664684200001

JCR分区：Q1

影响因子：6.1

年份：2021

卷号：21

期号：15

开始页：3004

结束页：3018

文献类型：Article

关键词：　

摘要："Breast cancer metastasis is a complex process controlled by multiple factors, including various cell-cell interactions, cell-environment coupling, and oxygen, nutrient and drug gradients that are intimately related to the heterogeneous breast tissue structure. In this study, we constructed a high-throughput in vitro biochip system containing an array of 642 microchambers arranged in a checkerboard configuration, with each chamber embedded in a composite extracellular matrix (ECM) composed of engineered collagen and Matrigel to mimic local heterogeneous environment in vivo. In addition, a controllable complex tetragonal chemical concentration profile can be achieved by imposing chemical compounds at the four boundaries of the chip, leading to distinct local nutrient and/or drug gradients in the individual microchambers. Here, the microchamber array with composite ECM (MACECM) device aims to simulate multiple tumor cell niches composed of both breast epithelial cells (MCF-10A-GFP) and metastatic breast cancer cells (MDA-MB-231-RFP), which enables systematic studies of cell responses to a variety of biochemical conditions. The results obtained from the MACECM studies indicate that discoidin domain receptor 1 (DDR1) inhibitor 7rh and matrix metalloproteinase inhibitor batimastat, in association with epidermal growth factor (EGF) had no significant effects on the growth of MCF-10A-GFP cells, but had significant effects on DDR1 expression and the related migratory behavior of MDA-MB-231-RFP cells. The MACECM design not only enables the construction of a more realistic in vitro model for investigating cancer cell migration mechanisms but also has considerable potential for further development as a platform for next-generation high-throughput and therapeutic screening (e.g., anti-cancer drug evaluation) and personalized medicine."

基金机构："National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [11974066, 11674043, 81172066, 81472858, 11704404]; NSFCNational Natural Science Foundation of China (NSFC) [915291003]; Fundamental and Advanced Research Program of Chongqing [cstc2019jcyj-msxmX0477]; Fundamental Research Funds for the Central UniversitiesFundamental Research Funds for the Central Universities [2019CDYGYB007]; Capital Health Development Research Project [2020-2-2072]; A Start-up Fund [08-1286-001]; 2nd Affiliated Hospital, Chongqing Medical University, Chongqing, P.R. China [2209-16]; Arizona State University"

基金资助正文："We gratefully acknowledge support by the National Natural Science Foundation of China (11974066, 11674043, 81172066, 81472858, 11704404) and a major research project award from the NSFC (915291003), the Fundamental and Advanced Research Program of Chongqing (cstc2019jcyj-msxmX0477), the Fundamental Research Funds for the Central Universities (2019CDYGYB007) and the Capital Health Development Research Project (Grant No. 2020-2-2072), A Start-up Fund (08-1286-001) and the Fund for ""Innovative Team on Cancer Metabolism"" (2209-16) from the 2nd Affiliated Hospital, Chongqing Medical University, Chongqing, P.R. China. In addition, we would like to thank Miss Qin Deng at the Analytical and Testing Center of Chongqing University for her assistance with immunofluorescence imaging and analysis. Y. J. thanks the Arizona State University for support and Peking University for hospitality during his sabbatical leave."