Cancer-associated fibroblasts regulate the plasticity of lung cancer stemness via paracrine signalling (Nat Commun. 2014 Mar 25;5:3472.)

報告日期: 2014/10/17
報告時間: 3:10/4:00
報告學生: 蔡鐙墴(以英文報告)
講評老師: 張南山
附件下載: 下載[1417-1411983626-1.pdf]  下載[1417-1411983626-2.pdf] 

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

Wan-Jiun Chen, Chao-Chi Ho, Yih-Leong Chang, Hsuan-Yu Chen, Chih-An Lin, Thai-Yen Ling, Sung-Liang Yu, Shin-Sheng Yuan, Yu-Ju Louisa Chen, Chien-Yu Lin, Szu-Hua Pan, Han-Yi Elizabeth 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.

Nat Commun. 2014 Mar 25;5:3472.

Speaker: Teng-Huang Tsai                                           Date: 2014.10.17

Commentator:Nan-Shan Chang, Ph.D.                                 Place: Room 602


Cancer stem cells (CSCs) are defined as a sub-population of tumors with the ability to self-renew, or differentiate to nontumorigenic cells. CSCs have been shown to be more resistant to chemotherapy and radiotherapy and possess metastatic potential. Due to these prior studies, CSCs become promising targets for development of new antitumor therapeutics. Although lung CSCs can be isolated from side populations (SPs) through specific markers such as CD133 and aldehyde dehydrogenase (ALDH), it remains difficult to maintain the stemness characteristics of CSCs in vitro for detailed studies.To maintain a quiescent state, most stem cells (for example, embryonic, induced pluripotent stem cells and even lung stem cells) depend on direct contact in the microenvironment or the presence of ‘feeder cells. In this study, the author established a sustainable primary culture of Oct3/4( + )/Nanog( + ) lung CSCs fed with CD90( + ) cancer-associated fibroblasts (CAFs) to further advance the knowledge of preserving CSCs in the tumor microenvironment. Even more, the author identified the paracrine network by which CAFs enrich CSCs through de-differentiation and reacquisition of stem cell-like properties. The authors had found out that IGF1R signaling activation in cancer cells in the presence of CAFs expressing IGF-II can induce Nanog expression and promote stemness. Moreover, this paracrine signaling predicts overall and relapse-free survival in stage I non-small cell lung cancer (NSCLC) patients. IGF-II/IGF1R signaling blockade inhibits Nanog expression and attenuates cancer stem cell features. This study demonstrated that CAFs constitute a supporting niche for cancer stemness, and targeting this paracrine signaling may present a new therapeutic strategy for NSCLC.


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