title: Transfer of the IL-37b gene elicits anti-tumor responses in mice bearing 4T1 breast cancer.
abstract: OBJECTIVE
  IL-37b has shown anti-cancer activities in addition to its anti-inflammatory properties. In this study, we investigated the effects of IL-37b on breast carcinoma growth in mice and to determine the involvement of T cell activation in the effects.
  
  
  METHODS
  IL-37b gene was transferred into mouse breast carcinoma cell line 4T1 (4T1-IL37b cells), the expression of secretory IL-37b by the cells was detected, and the effects of IL-37b expression on the cell proliferation in vitro was evaluated. After injection of 4T1 cells or 4T1-IL37b cells into immunocompetent BALB/c mice, immunodeficient BALB/c nude mice and NOD-SCID mice, the tumor growth and survival rate were measured. The proliferation of T cells in vitro was also detected.
  
  
  RESULTS
  IL-37b was detected in the supernatants of 4T1-IL37b cells with a concentration of 12.02 ± 0.875 ng/mL. IL-37b expression did not affect 4T1 cell proliferation in vitro. BALB/c mice inoculated with 4T1-IL37b cells showed significant retardation of tumor growth. BALB/c mice inoculated with both 4T1 cells and mitomycin C-treated 4T1-IL37b cells also showed significant retardation of tumor growth. But the anti-cancer activity of IL-37b was abrogated in BALB/c nude mice and NOD-SCID mice inoculated with 4T1-IL37b cells. Recombinant IL-37b slightly promoted CD4(+) T cell proliferation without affecting CD8(+) T cell proliferation.
  
  
  CONCLUSIONS
  IL-37b exerts anti-4T1 breast carcinoma effects in vivo by modulating the tumor microenvironment and influencing T cell activation.
authors.affiliation: 1] State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Disease, Chinese Academy of Medical Sciences, Tianjin 300020, China [2] Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, Tianjin 300052, China.
authors.forename: Wei-qiang
authors.initials: WQ
authors.lastname: Wang
authors.affiliation: College of Pharmacy, Liaoning University of Traditional Chinese Medicine, Shenyang 116600, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Zhao
authors.affiliation: Department of Respiratory Medicine, the Second Affiliated Hospital of Nanchang University, Nanchang 330006, China.
authors.forename: Yu-shan
authors.initials: YS
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Disease, Chinese Academy of Medical Sciences, Tianjin 300020, China.
authors.forename: Xiao-yu
authors.initials: XY
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Disease, Chinese Academy of Medical Sciences, Tianjin 300020, China.
authors.forename: Zhi-na
authors.initials: ZN
authors.lastname: Sun
authors.affiliation: Department of Respiratory Medicine, the Second Affiliated Hospital of Nanchang University, Nanchang 330006, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Yu
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Disease, Chinese Academy of Medical Sciences, Tianjin 300020, China.
authors.forename: Wan-tong
authors.initials: WT
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Disease, Chinese Academy of Medical Sciences, Tianjin 300020, China.
authors.forename: Song
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Respiratory Medicine, the Second Affiliated Hospital of Nanchang University, Nanchang 330006, China.
authors.forename: Jiu-long
authors.initials: JL
authors.lastname: Kuang
authors.affiliation: 1] Department of Respiratory Medicine, the Second Affiliated Hospital of Nanchang University, Nanchang 330006, China [2] Nanlou Department of Pulmonary Medicine, Beijing 301 Hospital, Beijing 100853, China.
authors.forename: Guo-gang
authors.initials: GG
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Disease, Chinese Academy of Medical Sciences, Tianjin 300020, China.
authors.forename: Zhong-chao
authors.initials: ZC
authors.lastname: Han
authors.affiliation: Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, Tianjin 300052, China.
authors.forename: Bang-mao
authors.initials: BM
authors.lastname: Wang
authors.affiliation: College of Pharmacy, Liaoning University of Traditional Chinese Medicine, Shenyang 116600, China.
authors.forename: Jing-xian
authors.initials: JX
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Disease, Chinese Academy of Medical Sciences, Tianjin 300020, China.
authors.forename: Xiao-ming
authors.initials: XM
authors.lastname: Feng
mesh_terms: D000818:Animals; D001940:Breast / Q000378:metabolism / Q000473:pathology*; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D057809:HEK293 Cells; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics* / Q000627:therapeutic use*; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D008819:Mice, Nude; D016513:Mice, SCID; D011994:Recombinant Proteins / Q000235:genetics / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000166:cytology / Q000473:pathology
chemical_list: C508587:IL37 protein, human; D007375:Interleukin-1; D011994:Recombinant Proteins
references.citation: Clin Exp Immunol. 2013 Jun;172(3):410-6
references.pmid: 23600829
references.citation: Cytokine. 2001 Jan 7;13(1):1-7
references.pmid: 11145836
references.citation: Front Immunol. 2014 Apr 15;5:174
references.pmid: 24782871
references.citation: J Cancer Res Clin Oncol. 2012 Oct;138(10):1727-36
references.pmid: 22699929
references.citation: J Immunol. 2003 Jan 1;170(1):107-13
references.pmid: 12496389
references.citation: Chin Med J (Engl). 2012 Dec;125(23):4245-8
references.pmid: 23217394
references.citation: Cytokine. 2002 Apr 21;18(2):61-71
references.pmid: 12096920
references.citation: J Biol Chem. 2000 Apr 7;275(14):10308-14
references.pmid: 10744718
references.citation: Proc Natl Acad Sci U S A. 2014 Feb 18;111(7):2650-5
references.pmid: 24481253
references.citation: PLoS One. 2013;8(9):e74753
references.pmid: 24069344
references.citation: Nat Immunol. 2010 Nov;11(11):1014-22
references.pmid: 20935647
references.citation: Cancer Res. 2011 Aug 15;71(16):5393-9
references.pmid: 21724589
references.citation: PLoS One. 2011;6(9):e24241
references.pmid: 21935389
references.citation: Proc Natl Acad Sci U S A. 2010 Aug 24;107(34):15105-10
references.pmid: 20696918
references.citation: Sci Rep. 2014;4:5177
references.pmid: 24898887
references.citation: Hum Gene Ther. 1999 Nov 1;10(16):2667-72
references.pmid: 10566894
references.citation: Hum Gene Ther. 2000 Mar 20;11(5):693-9
references.pmid: 10757349
references.citation: Cell Physiol Biochem. 2014;33(6):1802-14
references.pmid: 24923759
references.citation: Semin Immunol. 2013 Dec 15;25(6):389-93
references.pmid: 24275600
references.citation: Cancer Immunol Immunother. 2014 May;63(5):419-35
references.pmid: 24514955
references.citation: J Interferon Cytokine Res. 2013 Apr;33(4):154-61
references.pmid: 23570381
references.citation: Eur Cytokine Netw. 2011 Sep;22(3):127-47
references.pmid: 22047735
references.citation: Proc Natl Acad Sci U S A. 2011 Oct 4;108(40):16711-6
references.pmid: 21873195
references.citation: Biochem J. 2004 Jul 15;381(Pt 2):503-10
references.pmid: 15046617
references.citation: FEBS Lett. 2004 Nov 5;577(1-2):93-100
references.pmid: 15527767
references.citation: Nature. 1995 Nov 2;378(6552):88-91
references.pmid: 7477296