Open AccessEnhanced gastric cancer growth potential of mesenchymal stem cells derived from gastric cancer tissues educated by CD 4 + T cells
Author(s) -
Xu Rongman,
Zhao Xiangdong,
Zhao Yuanyuan,
Chen Bin,
Sun Li,
Xu Changgen,
Shen Bo,
Wang Mei,
Xu Wenrong,
Zhu Wei
Publication year - 2018
Publication title -
cell proliferation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.647
H-Index - 74
eISSN - 1365-2184
pISSN - 0960-7722
DOI - 10.1111/cpr.12399
Subject(s) - mesenchymal stem cell , propidium iodide , cancer cell , flow cytometry , apoptosis , microbiology and biotechnology , chemistry , cancer research , biology , cancer stem cell , cell growth , cancer , stem cell , programmed cell death , biochemistry , genetics
Abstract Objectives Gastric cancer mesenchymal stem cells (GC‐MSCs) can promote the development of tumour growth. The tumour‐promoting role of tumour‐associated MSC s and T cells has been demonstrated. T cells as the major immune cells may influence and induce a pro‐tumour phenotype in MSC s. This study focused on whether CD 4 + T cells can affect GC ‐ MSC s to promote gastric cancer growth. Materials and methods CD 4 + T cells upregulation of programmed death ligand 1 ( PD ‐L1) expression in GC ‐ MSC s through the phosphorylated signal transducer and activator of transcription (p‐ STAT 3) 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. CD 4 + T cell‐primed GC ‐ MSC s promoted GC growth in a subcutaneously transplanted tumour model in BALB /c nu/nu mice. Results Gastric cancer mesenchymal stem cells stimulated by activated CD 4 + T cells promoted migration of GC cells and enhanced GC growth potential in BALB /c nu/nu xenografts. PD ‐L1 upregulation of GC ‐ MSC s stimulated by CD 4 + T cells was mediated through the p‐ STAT 3 signalling pathway. CD 4 + T cells‐primed GC ‐ MSC s have greater GC volume and growth rate‐promoting role than GC ‐ MSC s, with cancer cell‐intrinsic PD ‐1/mammalian target of rapamycin ( mTOR ) signalling activation. Conclusions This study showed that GC ‐ MSC s are plastic. The immunophenotype of GC ‐ MSC s stimulated by CD 4 + T cells has major changes that may influence tumour cell growth. This research was based on the interaction between tumour cells, MSC s and immune cells, providing a new understanding of the development and immunotherapy of GC .