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Gastric-cancer-derived mesenchymal stem cells: a promising target for resveratrol in the suppression of gastric cancer metastasis

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Abstract

The tumor microenvironment (TM) is an essential factor of tumor progression. Mesenchymal stem cells (MSCs) are important components of the TM and play critical roles in cancer metastasis. Resveratrol (RES) is a potential antitumor drug that has attracted extensive attention. However, it remains unclear whether RES can exert its antitumor activity by targeting MSCs located in the TM. In this study, we demonstrated that the conditioned medium of gastric-cancer-derived MSCs (GC–MSCs) promoted gastric cancer (GC) metastasis and facilitated the progression of epithelialmesenchymal transition (EMT) of GC cells. However, after pretreatment with RES, the prometastatic effect of GC–MSCs on GC cells was reversed. Furthermore, RES reduced GC–MSC (IL-6, IL-8, MCP-1, VEGF) gene expression and protein secretion, and counteracted the activation of the GC–MSC-induced Wnt/β-catenin signaling of GC cells, with less β-catenin nuclear transport and declined expression of β-catenin, CD44, and CyclinD3 in GC cells. Re-expression of β-catenin impaired the inhibitory effect of RES on GC cells. In conclusion, RES restricted the mobility increase of GC cells and reversed the progress of EMT induced by GC–MSCs by inactivating the Wnt/β-catenin signaling. GC–MSCs are promising target for RES in the inhibition of GC metastasis.

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Abbreviations

GC:

Gastric cancer

GC–MSCs:

Gastric-cancer-derived mesenchymal stem cells

RES:

Resveratrol

GC–MSC–CM:

Conditioned medium of GC–MSCs

RES0-CM:

Conditioned medium of GC–MSCs pretreated with 0.4 ‰ DMSO for 24 h

RES20-CM:

Conditioned medium of GC–MSCs pretreated with 20 µM RES for 24 h

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Funding

This work was supported by the National Natural Science Foundation of China (81572075, 81702429), Natural Science Foundation of Jiangsu Province (BK20170561), Graduate Research and Innovation Projects of Jiangsu Province (KYCX17_1819), Practical innovation training program for college students of Jiangsu University (201810299579W) and Postdoctoral Research Foundation of China (2016M591791).

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Author notes

  1. Lei Yin and Rongxue Zhang contributed equally to this work.

Authors and Affiliations

  1. AoYoung Cancer Research Institute, Jiangsu University, Zhangjiagang, 215618, Jiangsu, China

    Lei Yin, Wenhao Li, Wenrong Xu & Hui Qian

  2. Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, 301 Xuefu Road, Zhenjiang, 212013, Jiangsu, China

    Lei Yin, Rongxue Zhang, Yuyan Hu, Maoye Wang, Zhaofeng Liang, Zixuan Sun, Wenrong Xu & Hui Qian

  3. Department of Clinical Laboratory Medicine, The Affiliated People’s Hospital of Jiangsu University, Zhenjiang, 212013, Jiangsu, China

    Runbi Ji

Authors
  1. Lei Yin
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  2. Rongxue Zhang
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  3. Yuyan Hu
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  4. Wenhao Li
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  6. Zhaofeng Liang
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  7. Zixuan Sun
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  8. Runbi Ji
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  9. Wenrong Xu
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  10. Hui Qian
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Contributions

LY, RZ and HQ designed and performed the research, and conducted data analysis and manuscript writing; YH, and ZL performed the apoptosis analysis and Transwell migration assay; WL and MW performed the western blot; and ZS, RJ, and WX provided technical guidance. All authors have read and approved the final manuscript for publication.

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Correspondence to Hui Qian.

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Conflict of interest

The authors declare that they have no competing interests.

Ethical approval

All procedures performed in studies involving animals were in accordance with the ethical standards of the medical ethics committee of Jiangsu University and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study were approved by the medical ethics committee of Jiangsu University (2012258).

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Informed consent was obtained from all individual participants included in the study.

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Yin, L., Zhang, R., Hu, Y. et al. Gastric-cancer-derived mesenchymal stem cells: a promising target for resveratrol in the suppression of gastric cancer metastasis. Human Cell 33, 652–662 (2020). https://doi.org/10.1007/s13577-020-00339-5

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  • DOI: https://doi.org/10.1007/s13577-020-00339-5

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