title: Cyclooxygenase-2 in tumor-associated macrophages promotes metastatic potential of breast cancer cells through Akt pathway.
abstract: Tumor-associated macrophages (TAMs) promote cancer development and progression by releasing various cytokines and chemokines. Previously, we have found that the number of COX-2+TAMs was associated with lymph node metastasis in breast cancer. However, the mechanism remains enigmatic. In this study, we show that COX-2 in breast TAMs enhances the metastatic potential of breast cancer cells. COX-2 in TAMs induces MMP-9 expression and promotes epithelial-mesenchymal transition (EMT) in breast cancer cells. In addition, COX-2/PGE2induces IL-6 release in macrophages. Furthermore, we find that the activation of Akt pathway in cancer cells is crucial for the pro-metastatic effect of COX-2+TAMs by regulating MMP-9 and EMT. These findings indicate that TAMs facilitate breast cancer cell metastasis through COX-2-mediated intercellular communication.
authors.affiliation: Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China;; Department of Oncology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Gan
authors.affiliation: Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Zhu
authors.initials: Z
authors.lastname: Qiu
authors.affiliation: Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Huang
authors.affiliation: Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China;; Department of Endocrine and Breast Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Yunhai
authors.initials: Y
authors.lastname: Li
authors.affiliation: Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Huang
authors.affiliation: Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Tingxiu
authors.initials: T
authors.lastname: Xiang
authors.affiliation: Department of Pharmacology, Chongqing Medical University, Chongqing, China.
authors.forename: Jingyuan
authors.initials: J
authors.lastname: Wan
authors.affiliation: Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Tianli
authors.initials: T
authors.lastname: Hui
authors.affiliation: Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China;; Department of Endocrine and Breast Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Hongzhong
authors.initials: H
authors.lastname: Li
authors.affiliation: Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China;; Department of Endocrine and Breast Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Guosheng
authors.initials: G
authors.lastname: Ren
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics / Q000502:physiology; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D008264:Macrophages / Q000201:enzymology* / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D016513:Mice, SCID; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D014945:Wound Healing / Q000235:genetics / Q000502:physiology
chemical_list: D051546:Cyclooxygenase 2; D051057:Proto-Oncogene Proteins c-akt; D020780:Matrix Metalloproteinase 9
keywords: Tumor microenvironment; breast cancer; cyclooxygenase-2.; macrophages