title: Opposite Effects of M1 and M2 Macrophage Subtypes on Lung Cancer Progression.
abstract: 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.
authors.affiliation: Departments of Chest Medicine and Emergency Medicine, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Ang
authors.initials: A
authors.lastname: Yuan
authors.affiliation: Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Yi-Jing
authors.initials: YJ
authors.lastname: Hsiao
authors.affiliation: Institute of Statistical Science, Academia Sinica, Taipei, Taiwan.
authors.forename: Hsuan-Yu
authors.initials: HY
authors.lastname: Chen
authors.affiliation: Graduate Institute of Toxicology, National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Huei-Wen
authors.initials: HW
authors.lastname: Chen
authors.affiliation: Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Chao-Chi
authors.initials: CC
authors.lastname: Ho
authors.affiliation: Graduate Institute of Toxicology, National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Yu-Yun
authors.initials: YY
authors.lastname: Chen
authors.affiliation: Departments of Chest Medicine and Emergency Medicine, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Yi-Chia
authors.initials: YC
authors.lastname: Liu
authors.affiliation: Departments of Surgery, National Taiwan University Hospital, Taipei, Taiwan.|General Education Center, National Defense University, Taipei, Taiwan.
authors.forename: Tsai-Hsia
authors.initials: TH
authors.lastname: Hong
authors.affiliation: Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University College of Medicine, Taipei, Taiwan.|Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan.|Department of Pathology, National Taiwan University College of Medicine, Taipei, Taiwan.|Center for Optoelectronic Biomedicine, National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Sung-Liang
authors.initials: SL
authors.lastname: Yu
authors.affiliation: Institute of Biomedical Sciences, National Chung-Hsing University, Taichung, Taiwan.|Agricultural Biotechnology Center, National Chung-Hsing University, Taichung, Taiwan.
authors.forename: Jeremy J W
authors.initials: JJ
authors.lastname: Chen
authors.affiliation: Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Pan-Chyr
authors.initials: PC
authors.lastname: Yang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D015415:Biomarkers; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D016000:Cluster Analysis; D019008:Drug Resistance, Neoplasm; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D016130:Immunophenotyping; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D008297:Male; D051379:Mice; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D010641:Phenotype; D011379:Prognosis; D016016:Proportional Hazards Models
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers