Microfluidic system for modelling 3D tumour invasion intosurrounding stroma and drug screening

摘要

Tumour invasion into the surrounding stroma is a critical step in metastasis, and it is necessary toclarify the role of microenvironmental factors in tumour invasion. We present a microfluidic systemthat simulated and controlled multi-factors of the tumour microenvironment for three-dimensional(3D) assessment of tumour invasion into the stroma. The simultaneous, precise and continuousarrangement of two 3D matrices was visualised to observe the migration of cancer cell populations orsingle cells by transfecting cells with a fluorescent protein. A vascular endothelial layer was formed tosimulate transendothelial transport of nutrients, and its endothelial barrier function was verified bythe diffusion of 70 kDa fluorescein isothiocyanate (FITC)-Dextran in 3D matrices. Through highthroughputcell migration tracking observation and statistic evaluation, we clarified that cell density ofthe tumour directly determined its invasiveness. The results suggested that increased secretion of IL-6among both cancer cells(MDA-MB-231) and noncancerous cells(MCF-10A or HDF-n) after coculturecontributes to cancer cell invasiveness, and this was verified by an IL-6 inhibitor assay. Finally,the drug efficacy of paclitaxel was reflected as changes in cancer cell migration ability, viability, andmorphology. Together, our microfluidic devices could be a useful tool to study the mechanism oftumour invasion into the stroma and to screen anti-metastatic drugs.