Rongman Xu1,2, Xiangdong Zhao3, Yuanyuan Zhao1, Bin Chen1, Li Sun1, Changgen Xu3, Bo Shen4, Mei Wang1, Wenrong Xu1, Wei Zhu1. 1. School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, China. 2. Department of Clinical Laboratory, Haian People's Hospital, Haian, Jiangsu, China. 3. Zhenjiang Provincial Blood Center, Zhenjiang, Jiangsu, China. 4. Department of Oncology, Jiangsu Cancer Hospital, Affiliated to Nanjing Medical University, Nanjing, Jiangsu, China.
Abstract
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.
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.
Authors: Sonja Kleffel; Christian Posch; Steven R Barthel; Hansgeorg Mueller; Christoph Schlapbach; Emmanuella Guenova; Christopher P Elco; Nayoung Lee; Vikram R Juneja; Qian Zhan; Christine G Lian; Rahel Thomi; Wolfram Hoetzenecker; Antonio Cozzio; Reinhard Dummer; Martin C Mihm; Keith T Flaherty; Markus H Frank; George F Murphy; Arlene H Sharpe; Thomas S Kupper; Tobias Schatton Journal: Cell Date: 2015-09-10 Impact factor: 41.582
Authors: K Abiko; N Matsumura; J Hamanishi; N Horikawa; R Murakami; K Yamaguchi; Y Yoshioka; T Baba; I Konishi; M Mandai Journal: Br J Cancer Date: 2015-03-31 Impact factor: 7.640
Authors: Loryn Holokai; Jayati Chakrabarti; Taylor Broda; Julie Chang; Jennifer A Hawkins; Nambirajan Sundaram; Lydia E Wroblewski; Richard M Peek; Jiang Wang; Michael Helmrath; James M Wells; Yana Zavros Journal: PLoS Pathog Date: 2019-01-31 Impact factor: 6.823