A 3D biophysical model for cancer spheroid cell-enhanced invasion in collagen-oriented fiber microenvironment

doi:10.1088/1674-1056/ab9c02

Abstract The process of in situ tumors developing into malignant tumors and exhibiting invasive behavior is extremely complicated. From a biophysical point of view, it is a phase change process affected by many factors, including cell-to-cell, cell-to-chemical material, cell-to-environment interaction, etc. In this study, we constructed spheroids based on green fluorescence metastatic breast cancer cells MDA-MB-231 to simulate malignant tumors in vitro, while constructed a three-dimensional (3D) biochip to simulate a micro-environment for the growth and invasion of spheroids. In the experiment, the 3D spheroid was implanted into the chip, and the oriented collagen fibers controlled by collagen concentration and injection rate could guide the MDA-MB-231 cells in the spheroid to undergo directional invasion. The experiment showed that the oriented fibers greatly accelerated the invasion speed of MDA-MB-231 cells compared with the traditional uniform tumor micro-environment, namely obvious invasive branches appeared on the spheroids within 24 hours. In order to analyze this interesting phenomenon, we have developed a quantitative analyzing approach to explore strong angle correlation between the orientation of collagen fibers and invasive direction of cancer cell. The results showed that the oriented collagen fibers produced by the chip can greatly stimulate the invasion potential of cancer cells. This biochip is not only conducive to modeling cancer cell metastasis and studying cell invasion mechanisms, but also has the potential to build a quantitative evaluation platform that can be used in future chemical drug treatments.

Keywords: 3D biochip spheroids MDA-MB-231 cells oriented collagen fibers cancer cell invasion

Received: 29 April 2020
Revised: 22 May 2020
Accepted manuscript online: 12 June 2020

PACS:	87.18.Gh	(Cell-cell communication; collective behavior of motile cells)
	87.14.em	(Fibrils (amyloids, collagen, etc.))

Fund: Project supported by the National Natural Science Foundation of China (Grant Nos. 11974066 and 11674043), the Fundamental Research Funds for the Central Universities, China (Grant No. 2019CDYGYB007), and the Natural Science Foundation of Chongqing, China (Grant No. cstc2019jcyj-msxmX0477).

Corresponding Authors: Liyu Liu
E-mail: lyliu@cqu.edu.cn

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Miaomiao Hai(海苗苗), Yanping Liu(刘艳平), Ling Xiong(熊玲), Guoqiang Li(李国强), Gao Wang(王高), Hongfei Zhang(张鸿飞), Jianwei Shuai(帅建伟), Guo Chen(陈果), Liyu Liu(刘雳宇) A 3D biophysical model for cancer spheroid cell-enhanced invasion in collagen-oriented fiber microenvironment 2020 Chin. Phys. B 29 098702

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A 3D biophysical model for cancer spheroid cell-enhanced invasion in collagen-oriented fiber microenvironment

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