Investigating the Evolution of Cancer Stem Cells Fueled by Lactate in Nasopharyngeal Carcinoma

• Main Authors: I-Hsuan Chung, 鍾怡萱
• Other Authors: Yann-Jang Chen
• Format: Others
• Language: en_US
• Published: 2015
• Online Access: http://ndltd.ncl.edu.tw/handle/zm4myx

碩士 === 國立陽明大學 === 生命科學系暨基因體科學研究所 === 103 === Cancer stem cells (CSCs) are a subpopulation of tumor cells that possess ability of self-renewal and are considered as the main causes of tumor recurrence and metastasis. Cancer cells may acquire stemness properties from tumor microenvironments. High concentration of lactate accumulated in tumors has been reported in many researches, and the accumulation of lactate in solid tumors may be a pivotal event in the development of malignancies. Thus, our aims in this study are to investigate the role of lactate involving in regulating stemness properties and its possible mechanism. To understand the role of lactate in differentiated cancer cells, we treated NPC line, TW01 and HONE1 cells with 10 mM lactate to evaluate the expression of stemness and EMT genes by Western blot, RT-qPCR and immunofluorescence staining assay. Furthermore, we utilized behavior assay to examine whether these cells acquire CSC properties under lactate treatment. We found that lactate treatment not only stimulated expressions of stemness and EMT related genes but also increased the CD24high/CD44high CSC-like subpopulation in TW01 parental cells. We also found the expression of stemness and EMT related genes increased along with duration of lactate treatment. Moreover, through behavior assays, such as tumor sphere assay, migration assay and side population assay, we found that lactate treated cells poses more CSC properties. Collectively, these findings showed that lactate confers long-term self-renewal and therapeutic resistance in NPC cells. Thus, it implies that lactate, the high concentration metabolite in tumor microenvironment, can develop malignancy of NPC by reprograming differentiated cancer cells into CSCs.