胰腺癌
肝星状细胞
癌症研究
癌症
突变体
生物
癌细胞
基因
内分泌学
遗传学
作者
Yu Tanaka,Shin Hamada,Ryotaro Matsumoto,Keiko Taguchi,Masayuki Yamamoto,Atsushi Masamune
出处
期刊:American Journal of Physiology-gastrointestinal and Liver Physiology
[American Physiological Society]
日期:2021-10-01
卷期号:321 (4): G378-G388
被引量:9
标识
DOI:10.1152/ajpgi.00120.2021
摘要
It was previously identified that systemic Nrf2 deletion attenuates pancreatic cancer progression in a mutant K-ras/p53-expressing mouse model (KPC mouse). In this study, the type of cell that is responsible for the retarded cancer progression was elucidated. Human pancreatic cancers were first examined, and elevated expression of NRF2-target gene products in α-smooth muscle actin-positive cells was found, suggesting that pancreatic stellate cells (PSCs) are involved in this process. Closer examination of primary cultured PSCs from Nrf2-deleted mice revealed that the cells were less proliferative and retained a lower migration capacity. The conditioned medium of Nrf2-deleted PSCs exhibited reduced growth-stimulating effects in pancreatic cancer cells. KPC mouse-derived pancreatic cancer cells coinjected with wild-type PSCs developed significantly larger subcutaneous tumors in immunodeficient mice than those coinjected with Nrf2-deleted PSCs. These results demonstrate that Nrf2 actively contributes to the function of PSCs to sustain KPC cancer progression, thus, suggesting that Nrf2 inhibition in PSCs may be therapeutically important in pancreatic cancer.NEW & NOTEWORTHY This study identified that Nrf2 contributes to PSC activation. Nrf2 deletion in PSCs resulted in attenuation of cancer-promoting role. Nrf2 in PSCs could be an attractive therapeutic target in pancreatic cancer.
科研通智能强力驱动
Strongly Powered by AbleSci AI