A microfluidic-based device for study of transendothelial invasion of tumor aggregates in realtime

Circulating tumor aggregates exhibit a high metastatic potential and could potentially serve as an important target for cancer therapies. In this study, we developed a microfluidic model that reconstitutes and is representative of the principal components of biological blood vessels, including vessel cavity, endothelium, and perivascular matrix containing chemokines. Using this model, the transendothelial invasion of tumor aggregates can be observed and recorded in realtime. In this study we analyzed the extravasation process of salivary gland adenoid cystic carcinoma (ACC) cell aggregates. ACC aggregates transmigrated across the endothelium under the stimulation of chemokine CXCL12. The endothelial integrity was irreversibly damaged at the site of transendothelial invasion. The transendothelial invasion of ACC aggregates was inhibited by AMD3100, but the adhesion of ACC aggregates to the endothelium was not affected by the CXCR4 antagonist. This model allows for detailed study of the attachment and transendothelial invasion of tumor aggregates; thus, it would be a useful tool for analysis of the underlying mechanisms of metastasis and for testing novel anti-metastasis agents.