重编程
癌症研究
骨肉瘤
转移
纤维化
生物
病理
肌成纤维细胞
癌变
医学
癌症
细胞
遗传学
作者
Zhi‐Ying Wu,Junmei Zhao,Jian Lin,Chuan-Zhen Hu,Weibin Zhang,Wenlan Yang,Ji Zhang,Jiwang Zhang,Jiang Zhu
出处
期刊:Cell Reports
[Elsevier]
日期:2018-07-01
卷期号:24 (5): 1266-1277.e5
被引量:30
标识
DOI:10.1016/j.celrep.2018.06.103
摘要
It is well established that fibrotic remodeling of the tumor microenvironment favors tumorigenesis, but whether fibrosis underlies malignant progression in other ways is unclear. Here, we report that adaptive myofibroblastic reprogramming of osteosarcoma stem cells (OSCs) results in a critical advantage when establishing lung macro-metastases and spheroid growth but does not affect the growth of primary lesions or monolayer cultures. FGFR2 signaling in OSCs initiates fibrosis, whereas the resultant fibronectin (FN) auto-deposition sustains fibrogenic reprogramming and OSC growth, resembling the process employed by non-malignant myofibroblasts to cause tissue fibrosis. Furthermore, we provide evidence that nintedanib targets the pan FGFR-FN axis to disrupt lung metastasis without affecting the bone lesion growth of OSCs. Thus, myofibroblastic reprogramming of human OSCs in the lungs might represent a druggable trait for treating a deadly metastatic complication.
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