Oncotarget

Research Papers:

Interleukin-32α promotes the proliferation of multiple myeloma cells by inducing production of IL-6 in bone marrow stromal cells

Xuanru Lin, Li Yang, Gang Wang, Fuming Zi, Haimeng Yan, Xing Guo, Jing Chen, Qingxiao Chen, Xi Huang, Yi Li, Enfan Zhang, Wenjun Wu, Yang Yang, Donghua He, Jingsong He and Zhen Cai _

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Oncotarget. 2017; 8:92841-92854. https://doi.org/10.18632/oncotarget.21611

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Abstract

Xuanru Lin1,*, Li Yang1,*, Gang Wang2, Fuming Zi3, Haimeng Yan1, Xing Guo1, Jing Chen1, Qingxiao Chen1, Xi Huang1, Yi Li1, Enfan Zhang1, Wenjun Wu1, Yang Yang1, Donghua He1, Jingsong He1 and Zhen Cai1

1Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China

2Department of Hematology, People’s Hospital of Quzhou, Quzhou, Zhejiang, China

3Department of Hematology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China

*These authors have contributed equally to this work

Correspondence to:

Zhen Cai, email: [email protected]

Keywords: interleukin-32, IL-6, multiple myeloma, bone marrow stromal cells

Received: March 14, 2017    Accepted: August 17, 2017    Published: October 07, 2017

ABSTRACT

Multiple myeloma (MM) is a malignant plasma disease closely associated with inflammation. In MM bone marrow microenvironment, bone marrow stromal cells (BMSCs) are the primary source of interleukin-6 (IL-6) secretion, which promotes the proliferation and progression of MM cells. However, it is still unknown how the microenvironment stimulates BMSCs to secrete IL-6. Interleukin-32 (IL-32) is a newly identified pro-inflammatory factor. It was reported that in solid tumors, IL-32 induces changes in other inflammatory factors including IL-6, IL-10, and TNF-α. The aim of this study was to investigate the expression of IL-32 and the role of IL-32 in the MM bone marrow microenvironment. Our data illustrate that MM patients have higher expression of IL-32 than healthy individuals in both bone marrow and peripheral blood. We used ELISA and qRT-PCR to find that malignant plasma cells are the primary source of IL-32 production in MM bone marrow. ELISA and Western blot analysis revealed that recombinant IL-32α induces production of IL-6 in BMSCs by activating NF-κB and STAT3 signaling pathways, konckdown of IL-32 receptor PR3 inhibit this process. Knockdown of IL-32 by shRNA decreased the proliferation in MM cells that induced by BMSCs. In conclusion, IL-32 secreted from MM cells has paracrine effect to induce production of IL-6 in BMSCs, thus feedback to promote MM cells growth.


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