Microfluidic co-culture system for cancer migratory analysis and anti-metastatic drugs screening.

Shengli Mi,Shengli Mi,Wei Sun,Wei Sun,Wei Sun,Wei Sun,Yuanyuan Xu,Yuanyuan Xu,Zhengjie Wu,Zhengjie Wu,Min Zhang,Min Zhang,Zhichang Du,Zhichang Du,Xiang Qian

doi:10.1038/srep35544

Abstract

Tumour metastasis is an important reason for cancer death, and cancer cell migration is an important step in the process of tumour metastasis. Studying cancer cell migration is of great significance. Here, we present a novel microfluidic co-culture system and establish mild, moderate and severe cancer models by using HMEpiC and MDA-MB–231 cells to study cancer cell migration and anti-cancer drug screening. Using this device, we achieved high cell viability (over 90%) and a stable analysis of the migration ability of cancer cells. We observed that the density of the cancer cells determined the probability of the occurrence of metastatic cells and that the induction of normal cells affected the metastatic velocity of each cancer cell. We verified that the increase in the migration ability of MDA-MB-231 cells co-cultured with HMEpiC cells was relative to the increased secretion of IL-6 and that this was verified by an IL-6 inhibitor assay. This co-culture also led to decreased CK-14 secretion and morphological changes in HMEpiC cells. Finally, significant inhibition of paclitaxel and tamoxifen on cancer migration was observed. Taken together, our microfluidic device could be a useful tool for the quantitation of the migratory capability and anti-metastatic drug screening.

Highlights

Nguyen et al developed an impedance sensing-based microfluidic device to investigate the migration of breast cancer cells embedded in 3D matrices[24]
There are many studies regarding breast cancer migration based on microfluidic devices, and some scholars have established co-culture tumour models in microfluidic devices to solely study cancer cell migration[11,27], only a few studies have focused on the interaction between cells and studied the role of normal cells in breast cancer migration[10,28]
The area of the normal cell culture chamber in the mild cancer model and the area of the cancer cell culture chamber in the severe cancer model were twice the area of the last four chambers (Fig. 2(a)), and this design can guarantee the uniformity of cell density in the zone near the microchannel arrays when seeding a high density of cells

Summary

Introduction

Nguyen et al developed an impedance sensing-based microfluidic device to investigate the migration of breast cancer cells embedded in 3D matrices[24]. In different regions of a metastatic breast tumour (Fig. 1(a)), the densities of cancer cells and non-malignant cells are different, and the migration ability of cancer cells in these regions may be not the same. We present a novel microfluidic system to establish an in vitro co-culture model that mimics different regions of a metastatic breast tumour to study cancer cell migration and anti-cancer drug screening. By adding different concentrations of paclitaxel and tamoxifen, we studied the effect of the drugs on cancer cell migration. This microfluidic system provides a novel way to mimic the in vivo tumour microenvironment, which can be used to perform anti-metastatic drug screening at different cell densities in breast tumours

Methods

Results

Discussion

Conclusion