Nature communications, 2014-03, Vol.5 (1), p.3472-3472, Article 3472
2014
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- Autor(en) / Beteiligte
- Titel
- Cancer-associated fibroblasts regulate the plasticity of lung cancer stemness via paracrine signalling
- Ist Teil von
- Nature communications, 2014-03, Vol.5 (1), p.3472-3472, Article 3472
- Ort / Verlag
- London: Nature Publishing Group UK
- Erscheinungsjahr
- 2014
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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. Cancer stem cells are a sub-population of tumour cells but how they interact with the tumour microenvironment is unclear. Here, Chen et al. culture lung cancer stem cells with cancer-associated fibroblasts and delineate a signalling pathway between the two cells that helps maintain the cancer stem cell state.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 2041-1723eISSN: 2041-1723DOI: 10.1038/ncomms4472Titel-ID: cdi_proquest_miscellaneous_1510710950
- Format
- –
- Schlagworte
- 13/1, 13/100, 13/109, 13/21, 13/31, 13/51, 13/89, 13/95, 38/39, 38/47, 49/79, 631/67/1612, 631/67/71, 631/80/86, Adenocarcinoma - genetics, Adenocarcinoma - metabolism, Aged, Aged, 80 and over, Animals, Carcinoma, Squamous Cell - genetics, Carcinoma, Squamous Cell - metabolism, Cells, Cultured, Female, Fibroblasts - metabolism, Gene Expression Profiling, Homeodomain Proteins - genetics, Homeodomain Proteins - metabolism, Humanities and Social Sciences, Humans, Insulin-Like Growth Factor II - genetics, Insulin-Like Growth Factor II - metabolism, Lung cancer, Lung Neoplasms - genetics, Lung Neoplasms - metabolism, Male, Mice, Middle Aged, multidisciplinary, Nanog Homeobox Protein, Neoplasm Transplantation, Neoplastic Stem Cells - metabolism, Octamer Transcription Factor-3 - genetics, Octamer Transcription Factor-3 - metabolism, Paracrine Communication, Receptors, Somatomedin - genetics, Receptors, Somatomedin - metabolism, Science, Science (multidisciplinary), Small Cell Lung Carcinoma - genetics, Small Cell Lung Carcinoma - metabolism, Thy-1 Antigens - metabolism, Tumor Microenvironment