A microfluidic device for characterizing the invasion of cancer cells in 3‐D matrix
- 10 December 2009
- journal article
- general
- Published by Wiley in Electrophoresis
- Vol. 30 (24), 4285-4291
- https://doi.org/10.1002/elps.200900289
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.Keywords
This publication has 37 references indexed in Scilit:
- A platform for assessing chemotactic migration within a spatiotemporally defined 3D microenvironmentLab on a Chip, 2008
- Partitioning microfluidic channels with hydrogel to construct tunable 3-D cellular microenvironmentsBiomaterials, 2008
- Cortactin in tumor invasivenessCancer Letters, 2008
- Reorganisation of the dendritic actin network during cancer cell migration and invasionSeminars in Cancer Biology, 2008
- A perfusable 3D cell-matrix tissue culture chamber for in situ evaluation of nanoparticle vehicle penetration and transportBiotechnology & Bioengineering, 2007
- Generation of stable concentration gradients in 2D and 3D environments using a microfluidic ladder chamberBiomedical Microdevices, 2007
- Migration of tumor cells in 3D matrices is governed by matrix stiffness along with cell-matrix adhesion and proteolysisProceedings of the National Academy of Sciences of the United States of America, 2006
- A parallel-gradient microfluidic chamber for quantitative analysis of breast cancer cell chemotaxisBiomedical Microdevices, 2006
- Invadopodia: Specialized Cell Structures for Cancer InvasionClinical & Experimental Metastasis, 2006
- Matrix metalloproteinases and tumor metastasisCancer and Metastasis Reviews, 2006