The identification of lung cancer stem cells in malignant pleural effusion and studying their responses to interferon-γ

• Main Authors: Yu-TszLi, 李育慈
• Other Authors: Wu-Chou Su
• Format: Others
• Language: zh-TW
• Published: 2010
• Online Access: http://ndltd.ncl.edu.tw/handle/38786784171059481340

碩士 === 國立成功大學 === 生物化學研究所 === 98 === Lung cancer is the leading cause of cancer death in Taiwan. The majority of patients present with their illness in the advanced stages that preclude curative surgical resections. Though chemotherapy has clearly shown a clinically significant benefit, the improvement of survival is modest and chemoresistance often occurs. Finally, patients with metastatic disease ultimately died of their disease. Thus, novel therapy is needful. Recently, cancer stem cell (CSC) has been proved to exist in a variety of tumors, which contribute to tumor metastasis and drug resistance. In many types of human cancers, a group of side-population (SP) cells were found to possess CSC properties. Though the SP cells have also been identified in lung cancer, the characteristics of human lung cancer stem cell are still obscure. Malignant plural effusion (MPE) is a common complication of lung cancer. The metastatic properties and the clinical availability make cancer cells in MPE a reasonable source to study lung cancer stem cell. In the current study, we firstly tried to identify SP cells in MPEs from patients with lung cancer and then isolate the SP cells for finding markers of lung cancer stem cells. The SP cells exist in lung cancer cell lines-A549, H1650, AS2 and CL1-0 with various percentages. We also demonstrated the presence of SP population (0.41~14%) in MPEs from patients with lung cancer. However, we showed no difference in the expression of potential stem cell markers (CD44、CD166、CD133、ABCG2) between the SP and non-SP cells. There is no difference in the tumor spheroid formation and xenograft formation in SCID mice between SP and non-SP cells either. By Aldefluor assay, we found potential CSCs (ALDHbr cells) in lung cancer cell lines (A549, H1650, AS2 and CL1-0). The percentages of ALDHbr and SP cells in the cell lines, however, are not correlated well. Interestingly, we found interferon (IFN) treatment is able to modulate stem cell generation. The ratio of SP and ALDHbr cell decreased after long-term IFN-γ treatment in A549, H1650, and AS2 cell lines, but increased in CL1-0 cells. Furthermore, we founded the expression of Sox2 protein in CL1-0 is much higher than that of other cell lines. Therefore, Sox2 protein may modulate stem cell fate upon IFN stimulation. However, the results are preliminary, which require more studies to confirm. We did not successfully discover markers for lung cancer stem cells in the study, but we have developed methods to identify potential lung cancer stem cells. We also found that IFN treatment may influence stem cell fate and the phenomenon might be modified by the expression of Sox2 protein.