title: [Preliminary study of the inhibitory effect and mechanism of B16F10-ESAT-6-gpi/IL-21 vaccine on the pulmonary metastasis in mouse models of melanoma].
abstract: OBJECTIVE
  To investigate the effect and mechanism of B16F10-ESAT-6-gpi/IL-21 tumor cell vaccine on pulmonary metastasis in mouse model of melanoma.
  
  
  METHODS
  Twelve 8-week old female C57BL/6 mice were used in this study. The mice were injected with wild-type B16F10 cells through tail vein after immunization with B16F10-ESAT-6-gpi/IL-21 tumor cell vaccine, and the pulmonary metastasis was observed. The CD4(+) and CD8(+) T cells were isolated by magnetic activated cell sorting, and then used for the detection of CFSE/7-AAD cytotoxicity by flow cytometry. Serum from the mice immunized with tumor-cell vaccine was used to detect IFN-γ expression by ELISA. The expression of TGF-β2, ZEB1, E-cadherin, and N-cadherin of tumor tissues was detected by RT-PCR and immunofluorescence, respectively.
  
  
  RESULTS
  The mice vaccinated with B16F10-ESAT-6-gpi/IL-21 had significantly fewer nodules in the lung and lower lung weight [(285.8 ± 19.01) mg vs. (406.3 ± 27.12) mg], with lower levels of TGF-β2, ZEB1 and N-cadherin proteins but higher level of E-cadherin protein within the tumor tissue, as compared with the control mice. Meanwhile, the immunized mice had significantly increased CD8(+) T cell killing activity [(42.62 ± 3.465)% vs. (22.29 ± 1.804)%] and IFN-γ expression level [(55.200 ± 7.173) pg/ml vs. (6.435 ± 1.339) pg/ml] over the control mice.
  
  
  CONCLUSIONS
  The B16F10-ESAT-6-gpi/IL-21 vaccine can inhibit the metastasis of melanoma in the lung in vaccinated melanoma-bearing mice. This inhibitory effect is associated with CD8(+) T cell immune response and a higher level of IFN-γ, which may influence on the mesenchymal-epithelial transition of tumor cells.
authors.affiliation: Department of Medicine, Nantong Cancer Hospital Affiliated to Nantong University, Nantong 226361, China.
authors.forename: Xiangfeng
authors.initials: X
authors.lastname: He
authors.forename: Wen
authors.initials: W
authors.lastname: Shi
authors.forename: Fengshu
authors.initials: F
authors.lastname: Zhao
authors.forename: Jianhong
authors.initials: J
authors.lastname: Wang
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Xu
authors.forename: Qinghe
authors.initials: Q
authors.lastname: Tan
authors.forename: Yongqiang
authors.initials: Y
authors.lastname: Sun
authors.forename: Dengyu
authors.initials: D
authors.lastname: Chen
authors.affiliation: Email: njdoujun@sina.cn.
authors.forename: Jun
authors.initials: J
authors.lastname: Dou
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D015820:Cadherins / Q000378:metabolism; D019496:Cancer Vaccines / Q000276:immunology*; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007378:Interleukins / Q000276:immunology; D008168:Lung / Q000473:pathology; D008175:Lung Neoplasms / Q000378:metabolism / Q000556:secondary*; D008545:Melanoma / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D009929:Organ Size; D014157:Transcription Factors / Q000378:metabolism; D053781:Transforming Growth Factor beta2 / Q000378:metabolism; D000071799:Zinc Finger E-box-Binding Homeobox 1; D000098546:Interleukin-21
chemical_list: D015820:Cadherins; D019496:Cancer Vaccines; D018398:Homeodomain Proteins; D007378:Interleukins; D014157:Transcription Factors; D053781:Transforming Growth Factor beta2; C486307:ZEB1 protein, human; D000071799:Zinc Finger E-box-Binding Homeobox 1; D007371:Interferon-gamma; D000098546:Interleukin-21