期刊
ONCOLOGY REPORTS
卷 22, 期 3, 页码 541-548出版社
SPANDIDOS PUBL LTD
DOI: 10.3892/or_00000469
关键词
reactive oxygen species; chloride intracellular channel 4; transforming growth factor-beta 1; tumour and stroma interaction; myofibroblasts
类别
资金
- National Natural Science Foundation of China [30571953]
- National Health and Medical research Council/Cancer council Queensland [401681]
Stromal myofibroblasts, activated by crosstalk signaling between the tumour and stroma, play a critical role in tumour development and progression. Chloride intracellular channel 4 (CLIC4) may be functionally import for tumour stromal fibroblast-to-myofibroblast transdifferentiaton, but the molecular mechanism of the process has not been addressed. In this study, the expression of CLIC4 in ovarian cancer tissues was analyzed by immunohistochemistry, and we used an indirect co-culture model of ovarian cancer cells and normal fibroblasts to demonstrate the molecular pathway in which CLIC4 participated during the fibroblast-to-myofibroblast transdifferentiation. The results showed that the expression of CLIC4 in 96.7% of ovarian cancer stroma and correlated with the up-regulation of myofibroblast marker alpha-SMA. Conditioned medium from ovarian cancer cells (CM) or transforming growth factor-beta 1 (TGF-beta 1) increased cellular reactive oxygen species (ROS) levels in fibroblasts, which initiated up-regulation of CLIC4 expression, then resulted in myofibroblast conversion. Moreover, inhibition of CLIC4 significantly reduced the expressions of factors related to the phenotype and functions of myofibroblasts, such as alpha-SMA, VEGF and HGF. These results suggest that ROS-initiated CLIC4 up-regulation is required for TGF-beta 1-induced fibroblast-to-myofibroblast transdifferentiaton in ovarian cancer, indicating that inhibiting the CLIC4 might have therapeutic potential targeting tumour stroma.
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