Cancer-associated fibroblasts regulate the plasticity of lung cancer stemness via paracrine signalling. - Literature - Data resources

24668028

Cancer-associated fibroblasts regulate the plasticity of lung cancer stemness via paracrine signalling.

Nat Commun, 2014/3/25;5:3472.

Chen WJ^[1], Ho CC^[2], Chang YL^[3], Chen HY^[4], Lin CA^[5], Ling TY^[6], Yu SL^[5], Yuan SS^[4], Chen YJ^[4], Lin CY^[4], Pan SH^[7], Chou HY^[8], Chen YJ^[9], Chang GC^[10], Chu WC^[11], Lee YM^[11], Lee JY^[11], Lee PJ^[11], Li KC^[12], Chen HW^[13], Yang PC^[14]

Affiliations

1] Graduate Institute of Oncology, National Taiwan University Medical College, Taipei 10051, Taiwan [2] Graduate Institute of Toxicology, National Taiwan University Medical College, Taipei 10051, Taiwan [3] Institute of Statistical Science, Academia Sinica, Taipei 11529, Taiwan.
Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University Medical College, Taipei 10051, Taiwan.
Department of Pathology and Graduate Institute of Pathology, National Taiwan University Medical College, Taipei 10051, Taiwan.
Institute of Statistical Science, Academia Sinica, Taipei 11529, Taiwan.
Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University Medical College, Taipei 10051, Taiwan.
Department of Pharmacology, National Taiwan University Medical College, Taipei 10051, Taiwan.
Graduate Institute of Medical Genomics and Proteomics, National Taiwan University Medical College, Taipei 10051, Taiwan.
Graduate Institute of Oral Biology, National Taiwan University Dentistry College, Taipei 10051, Taiwan.
Graduate Institute of Chemistry, Academia Sinica, Taipei 10051, Taiwan.
1] Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei 112, Taiwan [2] Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung 40705, Taiwan.
Graduate Institute of Toxicology, National Taiwan University Medical College, Taipei 10051, Taiwan.
1] Institute of Statistical Science, Academia Sinica, Taipei 11529, Taiwan [2] Department of Statistics, University of California, Los Angeles, California 90095, USA.
1] Graduate Institute of Toxicology, National Taiwan University Medical College, Taipei 10051, Taiwan [2] Genome and Systems Biology Degree Program, National Taiwan University, Taipei 10051, Taiwan.
1] Graduate Institute of Oncology, National Taiwan University Medical College, Taipei 10051, Taiwan [2] Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University Medical College, Taipei 10051, Taiwan [3] Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan.

PMID: 24668028DOI: 10.1038/ncomms4472

Impact factor: 17.694

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.

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