Mesenchymal stem cells overexpressing Sirt1 inhibit prostate cancer growth by recruiting natural killer cells and macrophages

Yang Yu; Qingyun Zhang; Qinggui Meng; Chen Zong; Lei Liang; Xue Yang; Rui Lin; Yan Liu; Yang Zhou; Hongxiang Zhang; Xiaojuan Hou; Zhipeng Han; Jiwen Cheng

doi:10.18632/oncotarget.12737

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Research Papers: Immunology:

Mesenchymal stem cells overexpressing Sirt1 inhibit prostate cancer growth by recruiting natural killer cells and macrophages

Yang Yu, Qingyun Zhang, Qinggui Meng, Chen Zong, Lei Liang, Xue Yang, Rui Lin, Yan Liu, Yang Zhou, Hongxiang Zhang, Xiaojuan Hou, Zhipeng Han and Jiwen Cheng _

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Oncotarget. 2016; 7:71112-71122. https://doi.org/10.18632/oncotarget.12737

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Abstract

Yang Yu1,*, Qingyun Zhang1,*, Qinggui Meng1,*, Chen Zong2, Lei Liang2, Xue Yang2, Rui Lin1, Yan Liu3, Yang Zhou1, Hongxiang Zhang1, Xiaojuan Hou2, Zhipeng Han2 and Jiwen Cheng1

1 Department of Urology, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, People’s Republic of China

2 Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, People’s Republic of China

3 The Fifth Department of Chemotherapy, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, People’s Republic of China

* These authors have contributed equally to the work

Correspondence to:

Jiwen Cheng, email:

Zhipeng Han, email:

Keywords: prostate cancer; mesenchymal stem cells; Sirt1; nature killer cells; C-X-C motif chemokine ligand 10; Immunology and Microbiology Section; Immune response; Immunity

Received: December 20, 2015 Accepted: October 13, 2016 Published: October 18, 2016

Abstract

Prostate cancer (PCa) has become the second leading cause of male cancer-related mortality in the United States. Mesenchymal stem cells (MSCs) are able to migrate to tumor tissues, and are thus considered to be novel antitumor carriers. However, due to their immunosuppressive nature, the application of MSCs in PCa therapy remains limited. In this study, we investigated the effect of MSCs overexpressing an NAD-dependent deacetylase sirtuin 1 (MSCs-Sirt1) on prostate tumor growth, and we analyzed the underlying mechanisms. Our results show that MSCs accelerate prostate tumor growth, whereas MSCs-Sirt1 significantly suppresses tumor growth. Natural killer (NK) cells and macrophages are the prominent antitumor effectors of the MSCs-Sirt1-induced antitumor activity. IFN-γ and C-X-C motif chemokine ligand 10 (CXCL10) are highly expressed in MSCs-Sirt1 mice. The antitumor effect of MSCs-Sirt1 is weakened when CXCL10 and IFN-γ are inhibited. These results show that MSCs-Sirt1 can effectively inhibit prostate cancer growthrecruiting NK cells and macrophages in a tumor inflammatory microenvironment.

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Research Papers: Immunology:

Mesenchymal stem cells overexpressing Sirt1 inhibit prostate cancer growth by recruiting natural killer cells and macrophages

Abstract