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Cell Prolif. 2018 Apr;51(2):e12399. doi: 10.1111/cpr.12399. Epub 2017 Oct 22.

Enhanced gastric cancer growth potential of mesenchymal stem cells derived from gastric cancer tissues educated by CD4+ T cells.

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School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, China.
Department of Clinical Laboratory, Haian People's Hospital, Haian, Jiangsu, China.
Zhenjiang Provincial Blood Center, Zhenjiang, Jiangsu, China.
Department of Oncology, Jiangsu Cancer Hospital, Affiliated to Nanjing Medical University, Nanjing, Jiangsu, China.



Gastric cancer mesenchymal stem cells (GC-MSCs) can promote the development of tumour growth. The tumour-promoting role of tumour-associated MSCs and T cells has been demonstrated. T cells as the major immune cells may influence and induce a pro-tumour phenotype in MSCs. This study focused on whether CD4+ T cells can affect GC-MSCs to promote gastric cancer growth.


CD4+ T cells upregulation of programmed death ligand 1 (PD-L1) expression in GC-MSCs through the phosphorylated signal transducer and activator of transcription (p-STAT3) signalling pathway was confirmed by immunofluorescence, western blotting and RT-PCR. Migration of GC cells was detected by Transwell migration assay, and apoptosis of GC cells was measured by flow cytometry using annexin V/propidium iodide double staining. CD4+ T cell-primed GC-MSCs promoted GC growth in a subcutaneously transplanted tumour model in BALB/c nu/nu mice.


Gastric cancer mesenchymal stem cells stimulated by activated CD4+ T cells promoted migration of GC cells and enhanced GC growth potential in BALB/c nu/nu xenografts. PD-L1 upregulation of GC-MSCs stimulated by CD4+ T cells was mediated through the p-STAT3 signalling pathway. CD4+ T cells-primed GC-MSCs have greater GC volume and growth rate-promoting role than GC-MSCs, with cancer cell-intrinsic PD-1/mammalian target of rapamycin (mTOR) signalling activation.


This study showed that GC-MSCs are plastic. The immunophenotype of GC-MSCs stimulated by CD4+ T cells has major changes that may influence tumour cell growth. This research was based on the interaction between tumour cells, MSCs and immune cells, providing a new understanding of the development and immunotherapy of GC.

[Indexed for MEDLINE]

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