Cancer-associated fibroblasts regulate the plasticity for lung cancer stemness

• Main Authors: Wan-Jiun Chen, 陳菀均
• Other Authors: Pan-Chyr Yang
• Format: Others
• Language: en_US
• Published: 2014
• Online Access: http://ndltd.ncl.edu.tw/handle/86386878828410447203

博士 === 國立臺灣大學 === 腫瘤醫學研究所 === 102 === Lung cancer is the leading cause of cancer death in Taiwan and worldwide. After a lot of efforts for improving the survival, the prognosis remained bad. Recently, cancer stem cells (CSCs) theory is proposed for an intrinsic resistance of tumor to chemotherapy. Cancer is regarded as an organ because of hierarchically organized heterogeneous populations of cells and possible originate from its stem cells “cancer stem cells”. CSCs can be viewed to have the ability “stemness” as stem cells with true multipotency and asymmetric division that maintain self-renewal and differentiate to specialized cell types. It is becoming increasingly clear that CSCs not only exist in hematologic malignancy but also in solid tumor including lung cancer. Cancer stem cells (CSCs) are the key target to cure cancer; however, how the CSCs subpopulation could be maintained and preserving their stemness in the tumorous microenvironment remains unknown. To establish a culture system for maintaining cancer stemness is urgently needed. Here, we demonstrated that cancer-associated fibroblasts (CAFs) can play as feeders with exhibiting significantly elevated paracrine IGF-II, HGF and SDF1 to enrich and maintain the cancer stemness and tumorigenecity of lung cancer cells synergistically through IGF1R, Met and CXCR4 that expressed in cancer cells. Interestingly and applicability, blockage of the paracrine signaling with specific antibody or inhibitors could inhibit Nanog expression, cancer stemness and tumor growth. The Cox regression analysis was performed to evaluate whether the IGF-II in CAFs; IGF1R and Nanog in cancer cells are independent prognostic factors. The Kaplan–Meier survival analysis was conducted to determine the association of the IGF-II, IGF1R and Nanog with overall survival and relapse-free survival. Our data demonstrate CAFs constitute the supporting niche for cancer stemness, and targeting this paracrine signaling may present a new therapeutic strategy for NSCLC.