Studying tumor extravasation using a microfluidic chip

Abstract

During extravasation, tumor cells adhere to the endothelial cell lining before transmigrating across the endothelial lining and basement membrane barrier. Ultimately, they invade the surrounding stroma to form new microcolonies. In this study, we have developed a microfluidic chip that resembles the blood vessel microenvironment by mimicking the basement membrane, the endothelial lining in the blood circulatory system and its surrounding connective tissue. To achieve this, a polydimethylsiloxane, PDMS microfluidic device was reproduced using replica moulding of a master fabricated by photolithography. This chip consisted of two microchannels separated by a row of microgaps. One of the microchannels was used to represent the blood capillary and the other microchannel was coated with Type I Collagen to represent the surrounding tissue. The row of microgaps was coated with Matrigel and lined with human microvascular endothelial cells, HMEC to represent the basement membrane and endothelial lining barrier respectively. With this device, it was found that the expression of pmaxGFP into HepG2 cells did not affect their migratory performance. However, the presence of the Matrigel and HMECs were found to significantly reduce the percentage of HepG2 cells migrating across the microgaps, suggesting the importance of their inhibitory role during cancer metastasis.