title: Opposite Effects of Coinjection and Distant Injection of Mesenchymal Stem Cells on Breast Tumor Cell Growth.
abstract: : Mesenchymal stem cells (MSCs) usually promote tumor growth and metastasis. By using a breast tumor 4T1 cell-based animal model, this study determined that coinjection and distant injection of allogeneic bone marrow-derived MSCs with tumor cells could exert different effects on tumor growth. Whereas the coinjection of MSCs with 4T1 cells promoted tumor growth, surprisingly, the injection of MSCs at a site distant from the 4T1 cell inoculation site suppressed tumor growth. We further observed that, in the distant injection model, MSCs decreased the accumulation of myeloid-derived suppressor cells and regulatory T cells in tumor tissues by enhancing proinflammatory factors such as interferon-γ, tumor necrosis factor-α, Toll-like receptor (TLR)-3, and TLR-4, promoting host antitumor immunity and inhibiting tumor growth. Unlike previous reports, this is the first study reporting that MSCs may exert opposite roles on tumor growth in the same animal model by modulating the host immune system, which may shed light on the potential application of MSCs as vehicles for tumor therapy and other clinical applications.
  
  
  
  Mesenchymal stem cells (MSCs) have been widely investigated for their potential roles in tissue engineering, autoimmune diseases, and tumor therapeutics. This study explored the impact of coinjection and distant injection of allogeneic bone marrow-derived MSCs on mouse 4T1 breast cancer cells. The results showed that the coinjection of MSCs and 4T1 cells promoted tumor growth. MSCs might act as the tumor stromal precursors and cause immunosuppression to protect tumor cells from immunosurveillance, which subsequently facilitated tumor metastasis. Interestingly, the distant injection of MSCs and 4T1 cells suppressed tumor growth. Together, the results of this study revealed the dual functions of MSCs in immunoregulation.
authors.affiliation: Program of Innovative Cancer Therapeutics, Department of Surgery, First Affiliated Hospital of Zhejiang University College of Medicine, Hangzhou, People's Republic of China.
authors.forename: Huilin
authors.initials: H
authors.lastname: Zheng
authors.affiliation: Department of Medical Oncology, Zhejiang Cancer Hospital, Hangzhou, People's Republic of China.
authors.forename: Weibin
authors.initials: W
authors.lastname: Zou
authors.affiliation: Program of Innovative Cancer Therapeutics, Department of Surgery, First Affiliated Hospital of Zhejiang University College of Medicine, Hangzhou, People's Republic of China.
authors.forename: Jiaying
authors.initials: J
authors.lastname: Shen
authors.affiliation: Program of Innovative Cancer Therapeutics, Department of Surgery, First Affiliated Hospital of Zhejiang University College of Medicine, Hangzhou, People's Republic of China Clinical Research Center, First Affiliated Hospital of Zhejiang University College of Medicine, Hangzhou, People's Republic of China.
authors.forename: Liang
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Biological Sciences, National University of Singapore, Singapore.
authors.forename: Shu
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas, USA Chinese Academy of Science Key Laboratory for Infection and Immunity, IBP-UTSW Joint Immunotherapy Group, Institute of Biophysics, Chinese Academy of Sciences, Beijing, People's Republic of China.
authors.forename: Yang-Xin
authors.initials: YX
authors.lastname: Fu
authors.affiliation: Program of Innovative Cancer Therapeutics, Department of Surgery, First Affiliated Hospital of Zhejiang University College of Medicine, Hangzhou, People's Republic of China Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, South Carolina, USA fanw@zju.edu.cn.
authors.forename: Weimin
authors.initials: W
authors.lastname: Fan
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000276:immunology* / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D007150:Immunohistochemistry; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D016133:Polymerase Chain Reaction
keywords: Breast tumor; Coinjection; Distant injection; Immunomodulatory; Mesenchymal stem cell