期刊
ACS BIOMATERIALS SCIENCE & ENGINEERING
卷 8, 期 2, 页码 598-609出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsbiomaterials.1c00558
关键词
matrix stiffness; sodium alginate; 3D culture; liver cancer stem cell; stemness; Yes-associated protein
资金
- Key Program of the National Natural Science Foundation of China [11832008]
Hepatocellular carcinoma tissue exhibits mechanical heterogeneity, with increasing stiffness from the core to the invasion front. Liver cancer stem cells (LCSCs), which preferentially enrich the invasion front, also demonstrate the highest stiffness in the tumor. A stiffer matrix significantly enhances LCSC stemness, potentially mediated by Yes-associated protein signaling. Our findings reveal the relationship between matrix stiffness and LCSC stemness, contributing to the development of novel treatment approaches for liver cancer.
A hepatocellular carcinoma tissue has mechanical heterogeneity, where the stiffness gradually increases from the core to the invasion front. Furthermore, there is evidence that stem cells from liver cancer (LCSCs) preferentially enrich the invasion front, exhibiting the stiffest modulus in the tumor. LCSCs have the features of stem/ progenitor cells and play a vital part in liver cancer development. However, whether matrix stiffness affects LCSC stemness remains unclear. Here, we established a threedimensional hydrogel for culturing LCSCs to simulate the stiffness of the core and the invasion front of a liver cancer tissue. The results showed that a stiffer matrix (72.2 +/- 0.90 kPa) significantly potentiated LCSC stemness as compared with a soft matrix (7.7 +/- 0.41 kPa). Moreover, Yes-associated protein signaling might mediate this promotion. Together, our findings illustrate the relationship between matrix stiffness and LCSC stemness, which may aid the production of novel treatment approaches against liver cancer.
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