Cancerous tumours can spread and infiltrate other tissues through blood vessels. This metastasis is driven by biochemical signals and a physical interaction with blood vessel endothelium. A critical step in this process is the invasion of the extracellular matrix (ECM) by cancer cells.
The ECM is a network of proteins, polysaccharides and growth factors that provide a platform for cell migration and act as supporting glue between cells. As of now, investigation of cancer metastasis through the ECM is held back by the lack of an effective model to study the physical interaction between cancerous and vascular cells, as well as by poor image resolution offered by current models, which do not allow quantification of the invasion process.
Microfluidic chip
Researchers from Boston University have now developed a microfluidic platform for modelling the infiltration of cancer cells into the ECM (Biofabrication 9 045001). This model exhibits cell migration without the use of biochemical gradients, while enabling imaging of cell–cell and cell–matrix interactions. The group used collagen hydrogels to model the ECM and monitored the migration and invasion of breast cancer cells. They established that incorporating endothelial cells into the model significantly boosted the rate of cancer cell invasion to the ECM, without the need for biochemical gradients to draw the cells across.
3D-design
Lead author Laura Blaha and colleagues used microfabrication techniques to create polydimethylsiloxane (PDMS) microfluidic chips with specific dimensions. These dimensions create a surface tension that restricts fluid flow between compartments, but allows cells to migrate and interact with the other cellular compartments.
Importantly, the thickness of the chip facilitated imaging of cells and their interactions. This is a big advantage over models commonly used to investigate tumour migration, which use transwell chamber devices, limiting the quality of images and the ability to draw effective conclusions from studies.
The platform enables staining of specific ECM and cell-cell interaction markers. Due to the chip’s straight, parallel channel design, protein staining protocols like the one described in the study can be completed with ease. This allowed the group to establish the production of ECM proteins from endothelial cells within the model.
Future applications
The authors predict that this model could be used in future experiments to probe the specific membrane proteins that enable the invasion of cancer cells to the ECM. A similar microfluidic model could also be used to model cell-cell and cell-matrix interactions for multiple diseases. The correct use of this microfluidic model might potentially lead to therapies for various diseases, including many different metastatic cancers.
