Opposite Effects of M1 and M2 Macrophage Subtypes on Lung Cancer Progression

被引:328
作者
Yuan, Ang [1 ,2 ]
Hsiao, Yi-Jing [3 ]
Chen, Hsuan-Yu [4 ]
Chen, Huei-Wen [5 ]
Ho, Chao-Chi [6 ]
Chen, Yu-Yun [5 ]
Liu, Yi-Chia [1 ,2 ]
Hong, Tsai-Hsia [7 ,8 ]
Yu, Sung-Liang [3 ,9 ,10 ,11 ]
Chen, Jeremy J. W. [12 ,13 ]
Yang, Pan-Chyr [6 ]
机构
[1] Natl Taiwan Univ Hosp, Dept Chest Med, Taipei, Taiwan
[2] Natl Taiwan Univ Hosp, Dept Emergency Med, Taipei, Taiwan
[3] Natl Taiwan Univ, Coll Med, Dept Clin Lab Sci & Med Biotechnol, Taipei 10764, Taiwan
[4] Acad Sinica, Inst Stat Sci, Taipei 11529, Taiwan
[5] Natl Taiwan Univ, Coll Med, Grad Inst Toxicol, Taipei 10764, Taiwan
[6] Natl Taiwan Univ, Coll Med, Dept Internal Med, Taipei, Taiwan
[7] Natl Taiwan Univ Hosp, Dept Surg, Taipei 100, Taiwan
[8] Natl Def Univ, Gen Educ Ctr, Taipei, Taiwan
[9] Natl Taiwan Univ Hosp, Dept Lab Med, Taipei, Taiwan
[10] Natl Taiwan Univ, Coll Med, Dept Pathol, Taipei, Taiwan
[11] Natl Taiwan Univ, Coll Med, Ctr Optoelect Biomed, Taipei 10764, Taiwan
[12] Natl Chung Hsing Univ, Inst Biomed Sci, Taichung 40227, Taiwan
[13] Natl Chung Hsing Univ, Agr Biotechnol Ctr, Taichung 40227, Taiwan
关键词
TUMOR-ASSOCIATED MACROPHAGES; CELL INVASION; SURVIVAL; ANGIOGENESIS; EXPRESSION; GROWTH; LYMPHANGIOGENESIS; MICROENVIRONMENT; ADENOCARCINOMA; INFILTRATION;
D O I
10.1038/srep14273
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];
摘要
Macrophages in a tumor microenvironment have been characterized as M1- and M2-polarized subtypes. Here, we discovered the different macrophages' impacts on lung cancer cell A549. The M2a/M2c subtypes promoted A549 invasion and xenograft tumor growth. The M1 subtype suppressed angiogenesis. M1 enhanced the sensitivity of A549 to cisplatin and decreased the tube formation activity and cell viability of A549 cells by inducing apoptosis and senescence. Different macrophage subtypes regulated genes involved in the immune response, cytoskeletal remodeling, coagulation, cell adhesion, and apoptosis pathways in A549 cells, which was a pattern that correlated with the altered behaviors of the A549 cells. Furthermore, we found that the identified M1/M2 gene signatures were significantly correlated with the extended overall survival of lung cancer patients. These results suggest that M1/M2 gene expression signature may be used as a prognostic indicator for lung cancer patients, and M1/M2 polarization may be a target of investigation of immune-modulating therapies for lung cancer in the future.
引用
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页数:12
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