title: Mesenchymal stem cells overexpressing Sirt1 inhibit prostate cancer growth by recruiting natural killer cells and macrophages.
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.
authors.affiliation: Department of Urology, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, People's Republic of China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of Urology, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, People's Republic of China.
authors.forename: Qingyun
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Urology, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, People's Republic of China.
authors.forename: Qinggui
authors.initials: Q
authors.lastname: Meng
authors.affiliation: Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, the Second Military Medical University, Shanghai, People's Republic of China.
authors.forename: Chen
authors.initials: C
authors.lastname: Zong
authors.affiliation: Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, the Second Military Medical University, Shanghai, People's Republic of China.
authors.forename: Lei
authors.initials: L
authors.lastname: Liang
authors.affiliation: Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, the Second Military Medical University, Shanghai, People's Republic of China.
authors.forename: Xue
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Urology, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, People's Republic of China.
authors.forename: Rui
authors.initials: R
authors.lastname: Lin
authors.affiliation: The Fifth Department of Chemotherapy, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Urology, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, People's Republic of China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Urology, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, People's Republic of China.
authors.forename: Hongxiang
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, the Second Military Medical University, Shanghai, People's Republic of China.
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Hou
authors.affiliation: Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, the Second Military Medical University, Shanghai, People's Republic of China.
authors.forename: Zhipeng
authors.initials: Z
authors.lastname: Han
authors.affiliation: Department of Urology, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, People's Republic of China.
authors.forename: Jiwen
authors.initials: J
authors.lastname: Cheng
mesh_terms: D000818:Animals; D002465:Cell Movement; D049109:Cell Proliferation; D054357:Chemokine CXCL10 / Q000502:physiology; D007371:Interferon-gamma / Q000502:physiology; D007694:Killer Cells, Natural / Q000502:physiology*; D008262:Macrophage Activation; D008264:Macrophages / Q000502:physiology*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011471:Prostatic Neoplasms / Q000473:pathology / Q000517:prevention & control*; D056564:Sirtuin 1 / Q000032:analysis / Q000502:physiology*
chemical_list: D054357:Chemokine CXCL10; C485433:Cxcl10 protein, mouse; D007371:Interferon-gamma; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1
keywords: C-X-C motif chemokine ligand 10; Immune response; Immunity; Immunology and Microbiology Section; Sirt1; mesenchymal stem cells; nature killer cells; prostate cancer