Enhanced gastric cancer growth potential of mesenchymal stem cells derived from gastric cancer tissues educated by CD4
| Autor: | Mei Wang, Wei Zhu, Changgen Xu, Li Sun, Yuanyuan Zhao, Xiangdong Zhao, Rongman Xu, Wenrong Xu, Bin Chen, Bo Shen |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
CD4-Positive T-Lymphocytes STAT3 Transcription Factor Mice Nude Biology B7-H1 Antigen 03 medical and health sciences Interleukin 21 Mice 0302 clinical medicine Stomach Neoplasms Cell Line Tumor Cytotoxic T cell Animals IL-2 receptor Antigen-presenting cell Interleukin 3 Cell Proliferation Mice Inbred BALB C CD40 ZAP70 TOR Serine-Threonine Kinases Mesenchymal Stem Cells Cell Biology General Medicine Original Articles Molecular biology Coculture Techniques Neoplasm Proteins 030104 developmental biology 030220 oncology & carcinogenesis Interleukin 12 biology.protein Neoplastic Stem Cells Signal Transduction |
| Zdroj: | Cell proliferation. 51(2) |
| ISSN: | 1365-2184 |
| Popis: | OBJECTIVES: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. |
| Databáze: | OpenAIRE |
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