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Inhibitory effect and molecular mechanism of mesenchymal stem cells on NSCLC cells

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Abstract

Non-small-cell lung cancer (NSCLC) is still the main threat of cancer-associated death. Current treatment of NSCLC has limited effectiveness, and unfortunately, the prognosis of NSCLC remains poor. Therefore, a novel strategy for cancer therapy is urgently needed. Stem cell therapy has significant potential for cancer treatment. Mesenchymal stem cells (MSCs) with capacity for self-renewal and differentiation into various cells types exhibit the feature of homing to tumor site and immunosuppression, have been explored as a new treatment for various cancers. Studies revealed that the broad repertoire of trophic factors secreted by MSCs extensively involved in the interplay between MSCs and tumor cells. In this study, we confirmed that MSCs do have the paracrine effect on proliferation and migration of NSCLC cells (A549, NCI-H460, and SK-MES-1). Co-culture system and conditioned medium experiments results showed that soluble factors secreted by MSCs inhibited the proliferation of NSCLC cells in vitro. The scratch assay showed that conditioned medium of MSCs could suppress the migration of NSCLC cells in vitro. Western blot results showed that the expression of proteins relevant to cell proliferation, anti-apoptosis, and migration was remarkably decreased via MAPK/eIF4E signaling pathway. We speculated that soluble factors secreted by MSCs might be responsible for inhibitory mechanism of NSCLC cells. By Human Gene Expression Microarray Assay and recombinant Vascular Endothelial Growth Factor 165 (VEGF165) neutralizing experiment, we verified that VEGF might be responsible for the down-regulation of proteins related to cell proliferation, anti-apoptosis, and migration by suppressing translation initiation factor eIF4E via MAPK signaling pathway. Taken together, our study demonstrated that a possible trophic factor secreted by MSCs could manipulate translation initiation of NSCLC cells via MAPK signaling pathway, and significantly affect the fate of tumor cells, which will be a new strategy for cancer therapy.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (81201762, 31371194). The authors thank Dr. Juan Du (Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet) for critical reading of the manuscript.

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Authors and Affiliations

  1. College of Life Sciences and Bioengineering, Beijing Jiaotong University, Beijing, 100044, People’s Republic of China

    Mengwu Pan, Lingling Hou, Jingsi Zhang, Diandian Zhao, Jilei Hua, Ziling Wang, Jinsheng He, Hong Jiang, Honggang Hu & Lishu Zhang

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  1. Mengwu Pan
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  2. Lingling Hou
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Pan, M., Hou, L., Zhang, J. et al. Inhibitory effect and molecular mechanism of mesenchymal stem cells on NSCLC cells. Mol Cell Biochem 441, 63–76 (2018). https://doi.org/10.1007/s11010-017-3174-y

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