Monocyte-derived factors including PLA2G7 induced by macrophage-nasopharyngeal carcinoma cell interaction promote tumor cell invasiveness
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Heng Boon Low1,2, Chin Wen Png1,2, Chunwei Li3, De Yun Wang4, Soon Boon Justin Wong1,2,5, Yongliang Zhang1,2
1Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117545, Singapore
2Immunology Programme, the Life Science Institute, National University of Singapore, Singapore 117597, Singapore
3Department of Otorhinolaryngology, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China
4Department of Otolaryngology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore
5Department of Pathology, National University Hospital, Singapore 119074, Singapore
Yongliang Zhang, email: [email protected]
Keywords: nasopharyngeal cancer, tumor associated macrophage, inflammation
Received: January 27, 2016 Accepted: June 29, 2016 Published: August 01, 2016
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.
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