title: The roles of P- and E-selectins and P-selectin glycoprotein ligand-1 in primary and metastatic mouse melanomas.
abstract: BACKGROUND
  Malignant melanoma is often accompanied by a host response of inflammatory cell infiltration that is highly regulated by multiple adhesion molecules.
  
  
  OBJECTIVE
  To evaluate the role of adhesion molecules, including P-selectin glycoprotein ligand-1 (PSGL-1), P-selectin, and E-selectin.
  
  
  METHODS
  Subcutaneous primary growth and metastasis to the lung of B16 melanoma cells were examined in mice lacking PSGL-1, P-selectin, or E-selectin.
  
  
  RESULTS
  Primary subcutaneous growth of B16 melanoma was augmented by loss of PSGL-1, P-selectin, or E-selectin, while pulmonary metastasis was reduced by the loss of E-selectin. The enhancement of subcutaneous tumor growth was associated with a reduced accumulation of natural killer cells, CD4(+) T cells and CD8(+) T cells, while the attenuation of pulmonary metastasis was related to the numbers of CD8(+) T cells. The expressions of transforming growth factor (TGF)-β and interleukin (IL)-6 were correlated with primary subcutaneous growth; TGF-β, IL-6, and interferon-γ were related to number of metastatic lung nodules. Cytotoxicity against melanoma cells in splenocytes and in tumor-draining lymph node cells were not defective by the absence of adhesion molecules, suggesting that the enhancement of tumor growth and metastasis caused by the loss of selectins results from an impaired migration of effector cells into the tissue.
  
  
  CONCLUSIONS
  The results indicate the complexity of anti-tumor responses mediated by adhesion molecules in primary subcutaneous tumors and pulmonary metastasis of murine experimental melanoma.
authors: Department of Dermatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors: Toshifumi
authors: T
authors: Yamaoka
authors: Manabu
authors: M
authors: Fujimoto
authors: Fumihide
authors: F
authors: Ogawa
authors: Ayumi
authors: A
authors: Yoshizaki
authors: Sang Jae
authors: SJ
authors: Bae
authors: Eiji
authors: E
authors: Muroi
authors: Kazuhiro
authors: K
authors: Komura
authors: Yohei
authors: Y
authors: Iwata
authors: Yuichiro
authors: Y
authors: Akiyama
authors: Koichi
authors: K
authors: Yanaba
authors: Kazuhiro
authors: K
authors: Shimizu
authors: Shinichi
authors: S
authors: Sato
mesh_terms: D000818:Animals; D016207:Cytokines / Q000235:genetics; D019040:E-Selectin / Q000502:physiology*; D007962:Leukocytes / Q000502:physiology; D008175:Lung Neoplasms / Q000556:secondary; D008297:Male; D008546:Melanoma, Experimental / Q000209:etiology* / Q000473:pathology; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D019007:P-Selectin / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D012878:Skin Neoplasms / Q000209:etiology* / Q000473:pathology
chemical_list: D016207:Cytokines; D019040:E-Selectin; D008562:Membrane Glycoproteins; D019007:P-Selectin; C084882:P-selectin ligand protein; D012333:RNA, Messenger