Citation: Song Chao, Gao Dan, Yuan Tianying, Chen Yongli, Liu Liping, Chen Xiaowu, Jiang Yuyang. Microfluidic three-dimensional biomimetic tumor model for studying breast cancer cell migration and invasion in the presence of interstitial flow[J]. Chinese Chemical Letters, ;2019, 30(5): 1038-1042. doi: 10.1016/j.cclet.2019.02.017 shu

Microfluidic three-dimensional biomimetic tumor model for studying breast cancer cell migration and invasion in the presence of interstitial flow

Song Chao ^a,b ,
Gao Dan ^a,b,*, ,
Yuan Tianying ^a,b ,
Chen Yongli ^a,b ,
Liu Liping ^c ,
Chen Xiaowu ^d ,
Jiang Yuyang ^a

a.
State Key Laboratory of Chemical Oncogenomics, The Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, China
b.
Key Laboratory of Metabolomics at Shenzhen, Shenzhen 518055, China
c.
Department of Hepatobiliary and Pancreatic Surgery, Shenzhen People's Hospital, Second Clinical Medical College of Jinan University, Shenzhen 518000, China
d.
Shenzhen Kivita Innovative Drug Discovery Institute, Shenzhen 518110, China

gao.dan@sz.tsinghua.edu.cn

Received Date: 23 January 2019
Revised Date: 18 February 2019
Accepted Date: 21 February 2019
Available Online: 22 May 2019

Figures(4)

Cell migration and invasion are critical steps in cancer metastasis, which are the major cause of death in cancer patients. Tumor-associated macrophages (TAMs) and interstitial flow (IF) are two important biochemical and biomechanical cues in tumor microenvironment, play essential roles in tumor progression. However, their combined effects on tumor cell migration and invasion as well as molecular mechanism remains largely unknown. In this work, we developed a microfluidic-based 3D breast cancer model by co-culturing tumor aggregates, macrophages, monocytes and endothelial cells within 3D extracellular matrix in the presence of IF to study tumor cell migration and invasion. On the established platform, we can precisely control the parameters related to tumor microenvironment and observe cellular responses and interactions in real-time. When co-culture of U937 with human umbilical vein endothelial cells (HUVECs) or MDA-MB-231 cells and tri-culture of U937 with HUVECs and MDA-MB-231 cells, we found that mesenchymal-like MDA-MB-231 aggregates activated the monocytes to TAM-like phenotype macrophages. MDA-MB-231 cells and IF simultaneously enhanced the macrophages activation by the stimulation of colony-stimulating factor 1 (CSF-1). The activated macrophages and IF further promoted vascular sprouting via vascular endothelial growth factor (VEGFα) signal and tumor cell invasion. This is the first attempt to study the interaction between macrophages and breast cancer cells under IF condition. Taken together, our results provide a new insight to reveal the important physiological and pathological processes of macrophages-tumor communication. Moreover, our established platform with a more mimetic 3D breast cancer model has the potential for drug screening with more accurate results.
- Microfluidics,
- Breast cancer,
- Tumor microenvironment,
- Cell migration and invasion,
- Interstitial flow
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