The role of Osteoprotegerin in stemness of lung cancer

• Main Authors: Yi-Han Chuang, 莊逸涵
• Other Authors: Kuang-Hui Sun
• Format: Others
• Language: zh-TW
• Published: 2013
• Online Access: http://ndltd.ncl.edu.tw/handle/55897018182799517616

碩士 === 國立陽明大學 === 醫學生物技術暨檢驗學系 === 101 === Lung cancer is the most common cause of cancer-related mortality worldwide, and the 5-year survival rate is less than 15%. The main reason of high mortality rate is due to the poor prognosis in early-stage lung cancer, the low response rate to chemotherapy and the high recurrence risk after treatment. It has been identified that a small subpopulation of distinct cancer cells (less than 5%), termed cancer stem cells (CSCs), has the abilities to self-renew and differentiate to multiple lineages. CSCs have been supposed to be responsible for chemoresistance, tumor recurrence and metastasis. So far, none of stemness-related genes are exclusively expressed by the solid tumor CSCs, highlighting the imperative to investigate more specific markers or to use combinational marker. In this study, to enrich lung CSCs, H1299 adenocarcinoma cell line was cultured in defined serum-free stem cell medium to grow as spheres. We confirmed the increased levels of stemness-related genes such as Oct4, Sox2, and Nanog, and clonogenicity in soft agar in H1299-CSCs. We found a novel molecule, osteoprotegrin (OPG) which is involved in bone remodeling intrinsically, was increased in primary and secondary spheres. Therefore, lentivirus-shRNA system was performed to suppress the expression level of OPG in H1299 cells. Knockdown of OPG was decreased in expression of stemness-related genes, sphere-forming ability, cell migration, cell invasion, and anchorage-independent growth ability, but did not affect cell proliferation in vitro. In addition, it was investigated that H1299-CSCs were highly resistant to cisplatin and paclitaxel, whereas suppression of OPG expression enhanced the sensitivity of CSCs to the two drugs. Our findings revealed that the role of OPG for maintaining stem-like properties and tumor progression in lung cancer, suggesting that OPG may be a potential molecular target for lung cancer treatment by eliminating cancer stem-like cells.