期刊
SCIENCE CHINA-MATERIALS
卷 62, 期 6, 页码 873-884出版社
SCIENCE PRESS
DOI: 10.1007/s40843-018-9383-3
关键词
stiffness; carcinoma-associated fibroblast; tumor microenvironment; chemotherapy; atomic force microscopy
资金
- Chinese Academy of Medical Sciences
- National Natural Science Foundation of China (NSFC) [31470905]
- National Institutes of Health/National Cancer Institute (NIH/NCI) [R21, CA208196]
- Peking Union Medical College
Carcinoma-associated fibroblasts (CAFs) function as a double-edged sword in tumor progression. However, factors affecting the transition between tumor promotion and inhibition remain to be investigated. Here, we found that the transition was determined by stiffness heterogeneity of the tumor stroma in which tumor cells and CAFs were grown. When tumor cells were grown on a rigid plastic substrate, supernatants from CAFs inhibited the cytotoxic effects of 5-fluorouracil. In contrast, when tumor cells were grown on a soft substrate (5.3 kPa), supernatants from CAFs grown on a soft substrate increased the cytotoxicity of 5-fluorouracil. The diverse effects of CAFs were mediated by mechanotransduction factors, including stroma stiffness-induced cytokine expression in CAFs and signal transduction associated with stress fiber formation of CAFs. Moreover, we found that the cytokine expression in CAFs was regulated by nuclear Yes-associated protein, which changed according to cell stiffness, as characterized by atomic force microscopy. Overall, these findings suggested that modulating the mechanotransduction of the stroma together with CAFs might be important for increasing the efficacy of chemotherapy.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据