Photolithography-free vessel-on-a-chip to simulate tumor cell extravasation

Abstract

A photolithography-free vessel-on-a-chip (VOC) to simulate tumor cell extravasation is presented. A microfluidic device integrated with two pieces of porous membranes was fabricated without using photolithography. The directional migration of MDA-MB-231 cells, a metastatic tumor cell line, was observed in the presence of a concentration gradient of fetal bovine serum (FBS). Migration assays toward CXCL12 demonstrated the directional migration of the cells in the presence of a concentration gradient of chemokines. The migration was inhibited by pre-incubating the cells with AMD3100, a known inhibitor. Transendothelial migration assays with human umbilical vein endothelial cells cultured on the porous membrane revealed that there is a delay time prior to the migration of MDA-MB-231 cells through the endothelial cell layer. The present VOC will be utilized to clarify the mechanism of transendothelial migration of tumor cells as well as to screen antimetastatic drug candidates.