An in vitro single cell assay for transendothelial migration of cancer cells

Metastasis is the leading cause of cancer related deaths. A critical component of metastasis is extravasation, which occurs following the adhesion of circulating tumor cells (CTCs) to the endothelium of target organs. The CTCs migrate through the endothelial layer and dense stroma, guided by an endogenously produced chemotactic gradients. Therefore, transendothelial migration (TEM) is a rate-limiting prerequisite for successful metastasis. Utilizing the microfluidic approach, we have developed a lab-on-a-chip platform to study TEM of the metastatic breast cancer cell line MDA-MB-231 in real-time and at the single cell level. The cells migrate across a gradient of stromal derived factor 1-α through a three-dimensional extracellular matrix mimicking the in vivo scenario and offering the ability to study signaling mechanisms involved in the transmigration of cancer as well as other motile cells.