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Cancer stem cells (CSCs) comprise a small portion of cancer cells, have greater self-renewal ability and metastatic potential than non-CSCs and are resistant to drugs and radiotherapy. CSCs and non-CSCs, which can reversibly change their stemness states, typically play roles in plasticity and cancer cell heterogeneity. Furthermore, the component that plays a key role in affecting CSC plasticity remains unknown. In this study, we utilized mechanically tunable polyacrylamide (PA) hydrogels to simulate different stiffnesses of the liver tissue matrix in various stages. Our results showed that hepatocellular carcinoma (HCC) cells were small and round in a soft matrix. The soft matrix increased the expression levels of liver cancer cells with stemness properties (LCSC) surface markers in HCC cells and the number of side population (SP) cells. Moreover, the soft matrix elicited early cell cycle arrest in the G1 phase and increased the cell sphere-forming ability. In addition, cells grown on the soft matrix showed enhanced chemoresistance and tumorigenicity potential. In summary, our study demonstrated that a soft matrix increases the stemness of HCC cells.

A Soft Matrix Enhances the Cancer Stem Cell Phenotype of HCC Cells