Cancer-associated fibroblasts regulate the plasticity of lung cancer stemness via paracrine signalling
2014; Nature Portfolio; Volume: 5; Issue: 1 Linguagem: Inglês
10.1038/ncomms4472
ISSN2041-1723
AutoresWan-Jiun Chen, Chao‐Chi Ho, Yih‐Leong Chang, Hsuan‐Yu Chen, Chih-An Lin, Thai‐Yen Ling, Sung‐Liang Yu, Shinsheng Yuan, Yu-Ju Louisa Chen, Chien–Yu Lin, Szu‐Hua Pan, Han‐Yi Chou, Yu‐Ju Chen, Gee‐Chen Chang, Wen-Cheng Chu, Yee-Ming Lee, Jen‐Yi Lee, Pei-Jung Lee, Ker-Chau Li, Huei‐Wen Chen, Pan‐Chyr Yang,
Tópico(s)Epigenetics and DNA Methylation
ResumoCancer stem cells (CSCs) are a promising target for treating cancer, yet how CSC plasticity is maintained in vivo is unclear and is difficult to study in vitro. Here we establish a sustainable primary culture of Oct3/4(+)/Nanog(+) lung CSCs fed with CD90(+) cancer-associated fibroblasts (CAFs) to further advance our knowledge of preserving stem cells in the tumour microenvironment. Using transcriptomics we identify the paracrine network by which CAFs enrich CSCs through de-differentiation and reacquisition of stem cell-like properties. Specifically, we find that IGF1R signalling activation in cancer cells in the presence of CAFs expressing IGF-II can induce Nanog expression and promote stemness. Moreover, this paracrine signalling predicts overall and relapse-free survival in stage I non-small cell lung cancer (NSCLC) patients. IGF-II/IGF1R signalling blockade inhibits Nanog expression and attenuates cancer stem cell features. Our data demonstrate that CAFs constitute a supporting niche for cancer stemness, and targeting this paracrine signalling may present a new therapeutic strategy for NSCLC.
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