Three-dimensional decellularized tumor extracellular matrices with different stiffness as bioengineered tumor scaffolds

Abstract

In the three-dimensional (3D) tumor microenvironment, matrix stiffness is associated with the regulation of tumor cells behaviors. <i>In vitro</i> tumor models with appropriate matrix stiffness are urgently desired. Herein, we prepare 3D decellularized extracellular matrix (DECM) scaffolds with different stiffness to mimic the microenvironment of human breast tumor tissue, especially the matrix stiffness, components and structure of ECM. Furthermore, the effects of matrix stiffness on the drug resistance of human breast cancer cells are explored with these developed scaffolds as case studies. Our results confirm that DECM scaffolds with diverse stiffness can be generated by tumor cells with different lysyl oxidase (LOX) expression levels, while the barely intact structure and major components of the ECM are maintained without cells. This versatile 3D tumor model with suitable stiffness can be used as a bioengineered tumor scaffold to investigate the role of the microenvironment in tumor progression and to screen drugs prior to clinical use to a certain extent.