title: Mesenchymal stem cells with Sirt1 overexpression suppress breast tumor growth via chemokine-dependent natural killer cells recruitment.
abstract: Mesenchymal stem cells (MSCs) are generally used in regenerative medicine, tissue engineering and therapy for immune disorder diseases. However, due to the immunosuppressive function of MSCs, the application of MSCs in breast cancer therapy remains limited. Sirt1 is the closest mammalian homologue of the yeast enzyme Sir2 which has an established capacity to influence yeast replicative lifespan. In this study, we demonstrated the effect of MSCs with Sirt1 overexpression (MSCs-Sirt1) in mice bearing 4T1 breast cancer and investigated the underlying mechanism. Firstly, we found that MSCs could accelerate breast tumor growth with promoted proliferation and inhibited apoptosis, whereas MSCs-Sirt1 significantly suppressed tumor growth with proliferation inhibition and apoptosis promotion. Moreover, we detected that NK cells were the prominent antitumor effectors for the MSCs-Sirt1-induced antitumor activity. Besides that, CXCL10 and IFN-γ showed the high level expression in MSCs-Sirt1 treatment group. The impulsive effect of MSCs-Sirt1 on 4T1 cells in vivo could be reversed by inhibition of CXCL10 and IFN-γ. Overall, our results suggest that MSCs-Sirt1 can effectively inhibit breast tumor growth via the recruitment of NK cells in tumor inflammatory microenvironment.
authors: Department of Urology, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, People's Republic of China.
authors: Yang
authors: Y
authors: Yu
authors: The Fifth Department of Chemotherapy, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, People's Republic of China.
authors: Yan
authors: Y
authors: Liu
authors: Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, the Second Military Medical University, Shanghai, People's Republic of China.
authors: Chen
authors: C
authors: Zong
authors: Department of Thyroid Breast Surgery, Affiliated Hospital of Weifang Medical University, Weifang, People's Republic of China.
authors: Qingbo
authors: Q
authors: Yu
authors: Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, the Second Military Medical University, Shanghai, People's Republic of China.
authors: Xue
authors: X
authors: Yang
authors: Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, the Second Military Medical University, Shanghai, People's Republic of China.
authors: Lei
authors: L
authors: Liang
authors: Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, the Second Military Medical University, Shanghai, People's Republic of China.
authors: Fei
authors: F
authors: Ye
authors: The Fifth Department of Chemotherapy, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, People's Republic of China.
authors: Li
authors: L
authors: Nong
authors: The Fifth Department of Chemotherapy, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, People's Republic of China.
authors: Yuxian
authors: Y
authors: Jia
authors: The Fifth Department of Chemotherapy, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, People's Republic of China.
authors: Yongkui
authors: Y
authors: Lu
authors: Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, the Second Military Medical University, Shanghai, People's Republic of China.
authors: Zhipeng
authors: Z
authors: Han
mesh_terms: D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D054357:Chemokine CXCL10 / Q000378:metabolism; D018925:Chemokines / Q000378:metabolism; D005260:Female; D007371:Interferon-gamma / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology*; D008325:Mammary Neoplasms, Experimental / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000201:enzymology* / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism*; D059016:Tumor Microenvironment / Q000276:immunology; D015854:Up-Regulation
chemical_list: D054357:Chemokine CXCL10; D018925:Chemokines; C485433:Cxcl10 protein, mouse; C000611649:IFNG protein, mouse; D007371:Interferon-gamma; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1