|Title:||Cancer-associated fibroblasts regulate the plasticity of lung cancer stemness via paracrine signalling||Authors:||Chen, W.-J.
Louisa Chen, Y.-J.
Elizabeth Chou, H.-Y.
|Issue Date:||2014||Publisher:||NATURE PUBLISHING GROUP||Source:||Nature Communications||Journal Volume:||5||Journal Issue:||1||Abstract:||
Cancer 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. © 2014 Macmillan Publishers Limited. All rights reserved.
|Appears in Collections:||基因體暨蛋白體醫學研究所|
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