title: Elevated AEG-1 expression in macrophages promotes hypopharyngeal cancer invasion through the STAT3-MMP-9 signaling pathway.
abstract: Macrophages play a critical role in tumor invasion and metastasis, which remain major causes of mortality in patients with hypopharyngeal cancer. Here we investigate the effect of an oncogene, AEG-1 expressed in macrophages on the invasion of hypopharyngeal cancer cells. AEG-1 is more highly expressed in macrophages of human hypopharyngeal cancer samples compared with adjacent non-tumor controls. Using matrigel invasion assay system, THP-1-derived macrophages with forced AEG-1 overexpression enhance FaDu cell invasion whereas macrophages with AEG-1 silence inhibit. Matrix metalloproteinase 9 (MMP-9), which is important in tumor invasion and metastasis through degrading extracellular matrix, is up-reulated by AEG-1 partly through NF-κB p65 in macrophages. Intriguingly, macrophage AEG-1 also induces MMP-9 up-regulated expression in FaDu cells. Furthermore, macrophage AEG-1 activates signal transducer and activator of transcription 3 (STAT3) in FaDu cells, which is responsible for macrophage AEG-1-induced an increase in MMP-9 expression and invasion of FaDu cells. This is the first to demonstrate that macrophage AEG-1 promotes tumor invasion through up-regulation of MMP-9 in both macrophages and cancer cells. Thus, the results provide evidences that macrophage AEG-1 contributes to promotion of tumor invasion, and represents as a potential target in hypopharyngeal cancer therapy.
authors: Department of Otorhinolaryngology Head and Neck Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China.|Shandong Provincial Key Laboratory of Otology, Jinan, Shandong, China.
authors: Xiuxiu
authors: X
authors: Liu
authors: Department of Otorhinolaryngology Head and Neck Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China.
authors: Zhenghua
authors: Z
authors: Lv
authors: Department of Otorhinolaryngology Head and Neck Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China.
authors: Jidong
authors: J
authors: Zou
authors: Department of Otorhinolaryngology Head and Neck Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China.|Shandong Provincial Key Laboratory of Otology, Jinan, Shandong, China.
authors: Xianfang
authors: X
authors: Liu
authors: Department of Otorhinolaryngology Head and Neck Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China.
authors: Juke
authors: J
authors: Ma
authors: Department of Otorhinolaryngology Head and Neck Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China.
authors: Chengtao
authors: C
authors: Sun
authors: Department of Otorhinolaryngology Head and Neck Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China.
authors: Na
authors: N
authors: Sa
authors: Department of Otorhinolaryngology Head and Neck Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China.|Shandong Provincial Key Laboratory of Otology, Jinan, Shandong, China.
authors: Wei
authors: W
authors: Xu
mesh_terms: D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002465:Cell Movement; D006801:Humans; D007012:Hypopharyngeal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008264:Macrophages / Q000378:metabolism* / Q000473:pathology; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins; D009361:Neoplasm Invasiveness; D016601:RNA-Binding Proteins; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D000074084:THP-1 Cells
chemical_list: D015815:Cell Adhesion Molecules; C483039:MTDH protein, human; D008565:Membrane Proteins; D016601:RNA-Binding Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
keywords: AEG-1; MMP-9; cancer invasion; hypopharyngeal cancer; macrophages