Cancer Extravasation Dynamics in an In Vitro Blood Vessel Model
Extravasation of cancer cells from the blood vessel, which involves the trans-endothelial migration and tissue invasion, remains a less well understood process in cancer metastasis . Understanding the mechanisms underlying the extravasation process is of fundamental importance in developing therapeutic targets for the prevention of metastasis ,. The aim of this research is to investigate breast cancer extravasation in vitro, using a microfluidic system with adjustable biophysical and biochemical factors, to mimic the 3D in vivo vascular microenvironment. In particular, the device is fabricated to mimic the interface between the blood vessel wall and the surrounding extracellular matrix. Using this microfluidic system, breast cancer cell extravasation from the blood vessel to the artificially simulated extracellular matrix was observed. Combining this microfluidic platform with an automated image analysis algorithm, cancer cell morphological changes during the migration process were quantified and they were found to be microenvironment-dependent. In particular, cancer cells were observed to exhibit invadopodia-like protrusions during the invasion process and the presence of endothelial cells forming the vessel lumen was found to sustain the cancer cell invasion into the matrix.