3D lung cancer cell migration and extracellular matrix remodeling within microfluidic devices

Abstract

Microfluidic devices filled with hydrogels that mimic the extracellular matrix are powerful and versatile research tools to recapitulate the 3D tumor microenvironment and study cancer in vitro. In this work, H1299 NSCLC cell migration phenotype and dynamics are characterized in hydrogels that mimic different tumor microenvironments, from pure collagen matrices similar to connective tissue to mixed collagen-Matrigel matrices that approximate a disorganized basement membrane at the front of cancer invasion. The role of the microenvironment composition and mechanical properties, cell adhesion, MMP proteolytic activity and integrin surface expression in the migration behavior of H1299 lung cancer cells within these 3D matrices are explored and explained in light of what it is known about cell migration in 3D environments. Finally, the extracellular matrix remodeling caused by H1299 cells in the different microenvironments is quantified by measuring the ability of H1299 cells to degrade, align, and compact their surrounding matrix.