Abstract
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.
Highlights
Cancer is the second most serious disease in the world after cardiovascular disease
In this study, we investigated the effects of PA hydrogels on the stemness of Hepatocellular carcinoma (HCC) cells
Our results showed that the PA hydrogels had great mechanical characteristics and adjustable stiffnesses, 3
Summary
Cancer is the second most serious disease in the world after cardiovascular disease. Hepatocellular carcinoma (HCC) is one of the most common malignancies with a high mortality rate worldwide due to its resistance to chemotherapy and poor prognosis [1]. Liver cancer cells with stemness properties (LCSCs) comprise a small portion of HCC cells. LCSCs are insensitive to drugs and radiotherapy and play a key role in the metastasis and recurrence of HCC [2]. Cancer stem cells (CSCs) typically have plasticity, which means that CSCs and non-CSCs can reversibly transform between stem and non-stem cell states. CSC plasticity plays a key role in cancer progression and metastasis [3,4]. Previous studies have shown the importance of CSC plasticity, the underlying factors remain unknown
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