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Murine bone marrow stromal cells pulsed with homologous tumor-derived exosomes inhibit proliferation of liver cancer cells

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Abstract

Background

Increasing evidence shows that bone marrow stromal cells (BMSCs) have antitumor activities both in vitro and in animal models. Further studies fleshed out the supportive data that the antitumor activity of BMSCs could be markedly enhanced by cytokines such as IL-2 and IFN-β (interferon). However, powerful strategies to activate BMSCs other than by genetically engineering interventions are still required.

Methods

In this study, new methods of generating antitumor activities of murine marrow-originated MSCs pulsed with homologous tumor-derived exosomes (TEX) were explored to yield potent immune effectors against hepatocellular carcinoma cells in vitro.

Results

The results showed that BMSCs pulsed with exosomes and IFN-γ exhibited increased migration ability with a result of 163.22 ± 26.90 versus 129.89 ± 29.28 cells/HP by transwell determination (p < 0.05). The inhibition of homologous hepatocellular carcinoma cells line H22 cells by exosomes pulsed BMSCs was significantly increased by 41.9 % compared with control (p < 0.05), and flow cytometry analysis showed that the cell cycle of H22 cells was arrested in G0/G1 phase. Meanwhile, western blot analysis showed that PCNA protein expression in the supernatant of H22 cells was significantly decreased.

Conclusions

This study demonstrated that BMSCs pulsed with TEX could enhance its antitumor activities, which might be regarded as a novel promising antitumor treatment.

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Acknowledgments

This study was funded by Natural Science Foundation of China (NSFC) 30471995, National Basic Research Program of China 2009CB521700 (973 Program) and Capital Development Grant 2007-2053 Beijing.

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Author notes

  1. Jun Ren

    Present address: Capital Medical University Cancer Center, Beijing Shijitan Hospital, 10 Tieyi Road, Beijing, 100038, China

Authors and Affiliations

  1. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Medical Oncology, Peking University Cancer Hospital, Beijing Cancer Hospital and Institute, Beijing, China

    Bo Ma, Hanfang Jiang, Jun Jia, Lijun Di, Guohong Song, Jing Yu, Yulin Zhu, Zhihao Lu, Xiaoli Wang, Xinna Zhou & Jun Ren

  2. Duke-PKU Cancer Program, Department of Medical Oncology and Immunotherapy, Peking University Cancer Hospital/Beijing Cancer Hospital and Institute, 52 Fucheng Rd, Beijing, 100142, China

    Jun Ren

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  1. Bo Ma
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Correspondence to Jun Ren.

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Ma, B., Jiang, H., Jia, J. et al. Murine bone marrow stromal cells pulsed with homologous tumor-derived exosomes inhibit proliferation of liver cancer cells. Clin Transl Oncol 14, 764–773 (2012). https://doi.org/10.1007/s12094-012-0860-9

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  • DOI: https://doi.org/10.1007/s12094-012-0860-9

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