title: P-selectin enhances growth and metastasis of mouse mammary tumors by promoting regulatory T cell infiltration into the tumors.
abstract: OBJECTIVE
  P-selectin is an adhesion receptor that is mainly present on endothelial cells and platelets. We investigated the role of P-selectin in the regulation of different T cell subsets in the tumor microenvironment, and how that influences the growth and metastasis of mouse mammary cancer cell line 4T1 in Balb/c mice.
  
  
  METHODS
  The 4T1 cells (1×10(4) or 1×10(5)) were inoculated subcutaneously in the pre-shaved back skin of the P-selectin knockout (P-sel-/-) and wild-type (WT) mice. Mice were monitored twice weekly for the tumor growth measurements and survival studies. The tumors and the lungs were isolated for cytokine and T cell subset analyses at the end of the study.
  
  
  RESULTS
  Mice lacking P-selectin had reduced tumor burden, higher survival and reduced metastasis compared to WT mice. Loss of P-selectin inhibited the infiltration of regulatory T cells and reduced pro-inflammatory cytokines, such as IL-4, IL-10, and TGFβ in the tumors. Furthermore, the CD8+ T cells and effector CD4+ T cells were functional and exhibited enhanced infiltration into the tumors of P-selectin knockout mice compared to WT mice.
  
  
  CONCLUSIONS
  These results demonstrated that P-selectin is an important adhesion molecule vital for infiltration of regulatory T cells into the tumors. Thus, inhibiting P-selectin can have important therapeutic implications against breast cancer growth and metastasis.
authors: Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL, USA; Department of Genetics, University of Alabama at Birmingham, Birmingham, AL, USA.
authors: Tahseen H
authors: TH
authors: Nasti
authors: Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL, USA; Department of Genetics, University of Alabama at Birmingham, Birmingham, AL, USA.
authors: Daniel C
authors: DC
authors: Bullard
authors: Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL, USA; Department of Genetics, University of Alabama at Birmingham, Birmingham, AL, USA. Electronic address: nabihayusuf@uabmc.edu.
authors: Nabiha
authors: N
authors: Yusuf
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D018836:Inflammation Mediators / Q000378:metabolism; D008325:Mammary Neoplasms, Experimental / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009362:Neoplasm Metastasis; D019007:P-Selectin / Q000235:genetics / Q000378:metabolism*; D015996:Survival Rate; D016176:T-Lymphocyte Subsets / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism*; D059016:Tumor Microenvironment
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D019007:P-Selectin
keywords: Breast cancer; Metastasis; P-selectin