A neutralized human LMP1-IgG inhibits ENKTL growth by suppressing the JAK3/STAT3 signaling pathway

Yuan Mao; Jun Wang; Mingzhi Zhang; Weifei Fan; Qi Tang; Siping Xiong; Xiaojun Tang; Juqing Xu; Lin Wang; Shu Yang; Suyao Liu; Li Xu; Yan Chen; Lin Xu; Rong Yin; Jin Zhu

doi:10.18632/oncotarget.14032

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Research Papers:

A neutralized human LMP1-IgG inhibits ENKTL growth by suppressing the JAK3/STAT3 signaling pathway

Yuan Mao, Jun Wang, Mingzhi Zhang, Weifei Fan, Qi Tang, Siping Xiong, Xiaojun Tang, Juqing Xu, Lin Wang, Shu Yang, Suyao Liu, Li Xu, Yan Chen, Lin Xu, Rong Yin and Jin Zhu _

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Oncotarget. 2017; 8:10954-10965. https://doi.org/10.18632/oncotarget.14032

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Abstract

Yuan Mao1,2,3,*, Jun Wang3,*, Mingzhi Zhang4, Weifei Fan3, Qi Tang5, Siping Xiong5, Xiaojun Tang5, Juqing Xu3, Lin Wang3, Shu Yang3, Suyao Liu3, Li Xu6, Yan Chen6, Lin Xu1,2, Rong Yin1,2, Jin Zhu7

1Department of Thoracic Surgery, Nanjing Medical University Affiliated Cancer Hospital, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Cancer Institute of Jiangsu Province, Nanjing, China

2The Fourth Clinical College of Nanjing Medical University, Nanjing, China

3Department of Hematology and Oncology, Department of Geriatric Lung Cancer Laboratory, Jiangsu Province Geriatric Hospital, Nanjing, China

4Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China

5Department of Pathology and The Key Laboratory of Antibody Technique of Ministry of Health, Nanjing Medical University, Nanjing, China

6Department of Pathology, Jiangsu Cancer Hospital, Nanjing, China

7Huadong Medical Institute of Biotechniques, Nanjing, China

*These authors contributed equally to this work

Correspondence to:

Lin Xu, email: [email protected]

Rong Yin, email: [email protected]

Jin Zhu, email: [email protected]

Keywords: LMP1, IgG, ENKTL, JAK/STAT

Received: October 19, 2016 Accepted: November 24, 2016 Published: December 20, 2016

ABSTRACT

Latent membrane protein 1 (LMP1), which is associated with the development of different types of Epstein-Barr virus (EBV) related lymphoma, has been suggested to be an important oncoprotein. In this study, a human anti-LMP1 IgG antibody (LMP1-IgG) was constructed and characterized by ELISA, western blotting (WB), affinity and immunohistochemistry (IHC) analyses. CCK-8, MTT, apoptosis assays, antibody-dependent cell-mediated cytotoxicity (ADCC) and CDC (complement-dependent cytotoxicity) assays were performed to evaluate the inhibitory effects of LMP1-IgG on extranodal nasal-type natural killer (NK)/T-cell lymphoma (ENKTL). Then, the influence of LMP1-IgG on the JAK/STAT signaling pathway was investigated. The results showed that the successfully constructed LMP1-IgG inhibited proliferation, induced apoptosis, and activated ADCC and CDC of ENKTL in a concentration- and time- dependent manner. Moreover, phosphorylation of JAK3 and STAT3 was inhibited by LMP1-IgG. Our data indicate that LMP1-IgG may provide a novel and promising therapeutic strategy for the treatment of LMP1-positive ENKTL.

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Research Papers:

A neutralized human LMP1-IgG inhibits ENKTL growth by suppressing the JAK3/STAT3 signaling pathway

Abstract