title: Monocyte-derived factors including PLA2G7 induced by macrophage-nasopharyngeal carcinoma cell interaction promote tumor cell invasiveness.
abstract: The non-keratinizing undifferentiated subtype of nasopharyngeal carcinoma (NPC) is a malignancy characterized by an intimate relationship between neoplastic cells and a non-neoplastic lymphoid component. Tumor-associated macrophages (TAMs) foster tumor progression through production of soluble mediators that support proliferation, angiogenesis, survival and invasion of malignant cells. However, the role of macrophages in the progression of NPC remains poorly understood. This study aims to investigate the functional and phenotypic changes that occur to macrophages in macrophage-NPC cell co-culture systems, and how these changes influence tumor cells. We found that monocytes, including THP-1 cells and primary human monocytes, co-cultured with C666-1 NPC cells upregulate expression of pro-inflammatory cytokines at the early stages, followed by the induction of metastasis-related genes and interferon-stimulated genes at the later stage of coculture, indicating that TAMs are "educated" by NPC cells for cancer progression. Importantly, the induction of these factors from the TAMs was also found to enhance the migratory capabilities of the NPC cells. We have also identified one of these macrophage-derived factor, phospholipase A2 Group 7 (PLA2G7), to be important in regulating tumor cell migration and a novel tumor-promoting factor in NPC. Further studies to characterize the role of PLA2G7 in tumor metastasis may help determine its potential as a therapeutic target in NPC.
authors.affiliation: Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117545, Singapore.|Immunology Programme, The Life Science Institute, National University of Singapore, Singapore 117597, Singapore.
authors.forename: Heng Boon
authors.initials: HB
authors.lastname: Low
authors.affiliation: Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117545, Singapore.|Immunology Programme, The Life Science Institute, National University of Singapore, Singapore 117597, Singapore.
authors.forename: Chin Wen
authors.initials: CW
authors.lastname: Png
authors.affiliation: Department of Otorhinolaryngology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China.
authors.forename: Chunwei
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Otolaryngology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore.
authors.forename: De Yun
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117545, Singapore.|Immunology Programme, The Life Science Institute, National University of Singapore, Singapore 117597, Singapore.|Department of Pathology, National University Hospital, Singapore 119074, Singapore.
authors.forename: Soon Boon Justin
authors.initials: SB
authors.lastname: Wong
authors.affiliation: Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117545, Singapore.|Immunology Programme, The Life Science Institute, National University of Singapore, Singapore 117597, Singapore.
authors.forename: Yongliang
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000502:physiology*; D002277:Carcinoma / Q000473:pathology*; D002450:Cell Communication; D045744:Cell Line, Tumor; D002465:Cell Movement; D018920:Coculture Techniques; D016207:Cytokines / Q000235:genetics; D006801:Humans; D008264:Macrophages / Q000502:physiology*; D009000:Monocytes / Q000502:physiology*; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000473:pathology*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis
chemical_list: D016207:Cytokines; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; C526684:PLA2G7 protein, human
keywords: inflammation; nasopharyngeal cancer; tumor associated macrophage