title: A microfluidic device for characterizing the invasion of cancer cells in 3-D matrix.
abstract: A microfluidic device was developed for the study of directed invasion of cancer cells in 3-D matrix with concentration gradient. This device consists of two parallel perfusion channels connected by two cell culture chambers. To mimic extracellular matrix (ECM), gelled basement membrane extract (BME) was used to support 3-D distribution of breast cancer cells (MCF7) in cell culture chambers. A stable linear concentration gradient of epidermal growth factor (EGF) was generated across the chambers by continuous perfusion. Using the device, we investigated MCF7 cell invasion induced by different concentrations of EGF in 3-D matrix. It was found that cancer cells responded to EGF stimulation with forming cellular protrusions and migrating towards high EGF concentration. We further investigated the anti-invasion effect of GM 6001, a matrix metalloproteinase inhibitor. We identified that matrix metalloproteinase inhibition repressed both cellular protrusion formation and cell migration in 3-D matrix. These findings suggest that EGF is able to induce MCF7 cell invasion in 3-D extracellular matrix and this effect is dependent on proteolytic activity. This device is relatively simple to construct and operate. It should be a useful platform for elucidating the mechanism of cancer invasion and screening anti-invasion drugs for cancer therapy.
authors.affiliation: Department of Biotechnology, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, P. R. China.
authors.forename: Tingjiao
authors.initials: T
authors.lastname: Liu
authors.forename: Chunyu
authors.initials: C
authors.lastname: Li
authors.forename: Hongjing
authors.initials: H
authors.lastname: Li
authors.forename: Shaojiang
authors.initials: S
authors.lastname: Zeng
authors.forename: Jianhua
authors.initials: J
authors.lastname: Qin
authors.forename: Bingcheng
authors.initials: B
authors.lastname: Lin
mesh_terms: D001943:Breast Neoplasms / Q000473:pathology; D045744:Cell Line, Tumor; D004815:Epidermal Growth Factor / Q000008:administration & dosage; D006801:Humans; D061965:Matrix Metalloproteinase Inhibitors; D044085:Microfluidics / Q000295:instrumentation*; D009361:Neoplasm Invasiveness; D011480:Protease Inhibitors / Q000008:administration & dosage
chemical_list: D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; D004815:Epidermal Growth Factor