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.
Highlights
Prostate cancer (PCa) is the most common cancer in men, and the second leading cause of male cancerassociated mortality [1, 2]
We applied subcutaneously implanted tumor model in C57BL/6 mice to determine the effect of Mesenchymal stem cells (MSCs)-Sirt1 on RM-1 and PC2 prostate cancer cells growth in vivo
At the end of experiment, we proved the existence of MSCs-Sirt1 in tumor tissues (Supplementary Figure 2)
Summary
Prostate cancer (PCa) is the most common cancer in men, and the second leading cause of male cancerassociated mortality [1, 2]. Staged and localized PCa can be well controlled by prostatectomy or radiotherapy. For advanced PCa, androgen deprivation therapy (ADT) is currently considered as the most effective treatment, giving a 70% initial effective rate [3]. There are still many PCa patients who are not responsive to ADT. Most androgen-responsive PCa patients develop androgen-resistant PCa after ADT. It is essential to find new effective strategies for PCa treatment
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