Mesenchymal stem cells overexpressing Sirt1 inhibit prostate cancer growth by recruiting natural killer cells and macrophages.
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.
['Yu|Yang|Y|', 'Zhang|Qingyun|Q|', 'Meng|Qinggui|Q|', 'Zong|Chen|C|', 'Liang|Lei|L|', 'Yang|Xue|X|', 'Lin|Rui|R|', 'Liu|Yan|Y|', 'Zhou|Yang|Y|', 'Zhang|Hongxiang|H|', 'Hou|Xiaojuan|X|', 'Han|Zhipeng|Z|', 'Cheng|Jiwen|J|']
D000818:Animals D002465:Cell Movement D049109:Cell Proliferation D054357:Chemokine CXCL10 D007371:Interferon-gamma D007694:Killer Cells, Natural D008262:Macrophage Activation D008264:Macrophages D008297:Male D059630:Mesenchymal Stem Cells D051379:Mice D008810:Mice, Inbred C57BL D011471:Prostatic Neoplasms D056564:Sirtuin 1
mesenchymal stem cells Sirt1 prostate cancer nature killer cells C-X-C motif chemokine ligand 10 Immune response Immunity Immunology and Microbiology Section