Targeting annexin A2 reduces tumorigenesis and therapeutic resistance of nasopharyngeal carcinoma.

Chang-Yu Chen,Chien-Ho Chen,Fei-Peng Lee,Yung-Feng Lin,Yung-Song Lin,Chia-Chun Kuo,Yin-Ju Chen,Yun-Tien Lin,Chi-Long Chen,Yu-Hsuan Sung,Chang-Fan Li,Jeng-Fong Chiou,Pin-Zhir Chao

doi:10.18632/oncotarget.4521

Abstract

The expression of annexin A2 (ANXA2) in nasopharyngeal carcinoma (NPC) cells induces the immunosuppressive response in dendritic cells; however, the oncogenic effect and clinical significance of ANXA2 have not been fully investigated in NPC cells. Immunohistochemical staining for ANXA2 was performed in 61 patients and the association with clinicopathological status was determined. Short hairpin (sh)RNA knockdown of ANXA2 was used to examine cellular effects of ANXA2, by investigating alterations in cell proliferation, migration, invasion, adhesion, tube-formation assay, and chemo- and radiosensitivity assays were performed. RT-qPCR, Western blotting, and immunofluorescence were applied to determine molecular expression levels. Clinical association studies showed that the expression of ANXA2 was significantly correlated with metastasis (p = 0.0326) and poor survival (p = 0.0256). Silencing of ANXA2 suppressed the abilities of cell proliferation, adhesion, migration, invasion, and vascular formation in NPC cell. ANXA2 up-regulated epithelial-mesenchymal transition associated signal proteins. Moreover, ANXA2 reduced sensitivities to irradiation and chemotherapeutic drugs. These results define ANXA2 as a novel prognostic factor for malignant processes, and it can serve as a molecular target of therapeutic interventions for NPC.

Highlights

Nasopharyngeal carcinoma (NPC) is the most common type of malignant tumor that occurs at the nasopharynx
The expression of annexin A2 (ANXA2) in nasopharyngeal carcinoma (NPC) cells induces the immunosuppressive response in dendritic cells; the oncogenic effect and clinical significance of ANXA2 have not been fully investigated in NPC cells
A proteomics comparison that analyzed an Epstein-Barr virus (EBV)-associated NPC cell line (C666–1) and normal nasopharyngeal cell line (NP69) showed that ANXA2 was downregulated in the NPC cell line and found that cytoplasmic staining, complete and incomplete membrane staining, and both cytoplasmic and membrane staining were all lost in clinical tissues [19]

Summary

Introduction

Nasopharyngeal carcinoma (NPC) is the most common type of malignant tumor that occurs at the nasopharynx. Available clinical therapies for NPC are radiotherapy, chemotherapy, and a combination of the two. Besides CTLs, other studies indicated the functions of dendritic cells (DCs) in cancer immunotherapy such as the tumor infiltrating DCs reflect on the prognosis and survival in NPC [9,10,11]. Through NPC cells and DCs interaction, DC functions are inhibited by a ligand, called annexin A2 (ANXA2), which allows NPC cells to escape from immune surveillance [12]. An immunosuppressive reaction might be the main way through which NPC escapes from attack by immune cells. We propose that ANXA2 may be a therapeutic target in NPC

Methods

Results

Conclusion