THREE-DIMENSIONAL CARCINOMA INVASIVE MODELS FOR DRUG DISCOVERY USING MICROFLUIDIC ASSAYS

Abstract

THE AIM OF THIS STUDY WAS TO DEVELOP A MICROFLUIDIC SYSTEM THAT INTEGRATES A TUMOR CELL MODEL IN A 3D HYDROGEL SCAFFOLD, IN CLOSE CO-CULTURE WITH AN ENDOTHELIAL MONOLAYER, MIMICKING THE IN VIVO TUMOR MICROENVIRONMENT. FIRST, A549 LUNG ADENOCARCINOMA MULTICELLULAR CANCER AGGREGATES (MCAS) WERE SUCCESSFULLY GENERATED USING A SIMPLE LASER ABLATION METHOD. FURTHER INTEGRATION OF MCAS WAS UTILIZED IN MICROFLUIDIC PLATFORMS WITH CO-CULTURE OF HUMAN UMBILICAL VEIN ENDOTHELIAL CELLS (HUVECS) VALIDATING 3D DRUG SCREENING ASSAY. LUNG A549 AND BLADDER CARCINOMA T24 MCAS WERE INVESTIGATED BY DOSE-RESPONSE ASSAYS ACCORDING TO THEIR INVASIVE CAPABILITY TO THE ADJACENT 3D MATRIX. THE ENHANCED DISPERSAL OF T24 IS A CONSEQUENCE OF THE SECRETION OF GROWTH FACTORS INCLUDING HGF AND FGF-2 BY HUVECS. OVERALL, THE ABOVE SYSTEMS, WITH RECAPITULATED MICROENVIRONMENT, ARE EXPECTED PROVIDE INSIGHTS FOR THE DEVELOPMENT OF FUTURE DRUG DISCOVERY.