Identification of drugs as single agents or in combination to prevent XXXX in a microfluidic 3D environment.

@entity1 @entity11968 @entity8096 @entity7242 @entity146 @entity5 @entity189 @entity540 @entity150 @entity2220 @entity2383
Experiments were performed in a modified microfluidic platform recapitulating part of the in vivo @entity5 microenvironment by co-culturing @entity189 cell aggregates embedded in a three-dimensional (3D) collagen scaffold with @entity1 umbilical vein endothelial cells (HUVECs). HUVECs were seeded in one channel of the @entity2383 in vitro prior to introducing the aggregates. The @entity2220 cell line A549 and the @entity150 cell line T24 were tested. Dose-response assays of four drugs known to interfere with Epithelial Mesenchymal Transition (EMT) signaling pathways were quantified using relative dispersion as a metric of EMT progression. The presence of HUVECs in one channel induces cell dispersal in A549 which then can be inhibited by each of the four drugs. Complete inhibition of T24 aggregate dispersal, however, is not achieved with any single agent, although partial inhibition was observed with 10  M of the @entity7242 inhibitor, @entity8096 . Almost complete inhibition of T24 dispersal in monoculture was achieved only when the four drugs were added in combination, each at 10  M concentration. Coculture of T24 with HUVECs forfeits the almost-complete inhibition. The enhanced dispersal observed in the presence of HUVECs is a consequence of secretion of growth factors, including @entity11968 and @entity540 , by endothelial cells. This 3D microfluidic co-culture platform provides an in vivo-like surrogate for anti-invasive and anti-metastatic drug screening. It will be particularly useful for defining combination therapies for @entity146 such as invasive @entity150 .
