title: IL-6 expression regulates tumorigenicity and correlates with prognosis in bladder cancer.
abstract: Identification of potential tumor markers will help stratify and identify a tumor's malignant potential and its response to specific therapies. IL-6 has been reported to be a predictor in various cancers. Therefore, the present study was performed to highlight the role of IL-6 in improving treatment and determining prognosis of bladder cancer. The human bladder cancer cell lines HT1376 and HT1197 were selected for cell and animal experiments, in which biological changes after experimental manipulation of IL-6 were explored, including tumor behavior and related signaling in bladder cancer. In addition, clinical specimens from 85 patients with muscle-invasive, and 50 with non-muscle invasive bladder cancers were selected for immunohistochemical staining to evaluate the predictive capacity of IL-6 in relation to clinical outcome. The data revealed that IL-6 was overexpressed in the bladder cancer specimens compared with non-malignant tissues at both mRNA and protein levels. Positive staining of IL-6 was significantly correlated with higher clinical stage, higher recurrence rate after curative treatment, and reduced survival rate. Tumor growth and invasive capability were attenuated when IL-6 was blocked. The underlying changes included decreased cell proliferation, less epithelial-mesenchymal transition (EMT), decreased DNA methyltransferase 1 expression and attenuated angiogenesis. In conclusion, our findings showed that IL-6 could be a significant predictor for clinical stage and prognosis of bladder cancer. Moreover, targeting IL-6 may be a promising strategy for treating bladder cancer.
authors: Department of Radiation Oncology, Chang Gung Memorial Hospital, Chiayi, Taiwan.
authors: Miao-Fen
authors: MF
authors: Chen
authors: Paul-Yang
authors: PY
authors: Lin
authors: Ching-Fang
authors: CF
authors: Wu
authors: Wen-Cheng
authors: WC
authors: Chen
authors: Chun-Te
authors: CT
authors: Wu
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D001743:Urinary Bladder / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D001749:Urinary Bladder Neoplasms / Q000098:blood supply / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology*
chemical_list: D015850:Interleukin-6; D012333:RNA, Messenger; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases
references: Curr Opin Pharmacol. 2009 Aug;9(4):396-404
references: 19596608
references: Histopathology. 2005 May;46(5):481-9
references: 15842629
references: J Clin Invest. 2007 Dec;117(12):3660-3
references: 18060028
references: Ann N Y Acad Sci. 2009 Aug;1171:59-76
references: 19723038
references: Urol Int. 2009;83(1):98-106
references: 19641368
references: Cancer Cell. 2004 Aug;6(2):111-6
references: 15324694
references: Mediators Inflamm. 2012;2012:528690
references: 22811589
references: J Urol. 2002 Mar;167(3):1475-81
references: 11832773
references: Immunol Rev. 2004 Dec;202:275-93
references: 15546400
references: J Urol. 1992 Sep;148(3):791-4
references: 1512827
references: J Natl Cancer Inst. 2012 Jun 20;104(12):899-905
references: 22572994
references: Cancer. 2011 Nov 15;117(22):5221-33
references: 21523767
references: Nat Rev Cancer. 2004 Feb;4(2):143-53
references: 14732866
references: Cancer Res. 2012 Jul 1;72(13):3135-42
references: 22532166
references: J Clin Oncol. 2001 Feb 1;19(3):666-75
references: 11157016
references: BMC Urol. 2012 Jun 13;12:18
references: 22695075
references: Head Neck. 2011 Aug;33(8):1132-43
references: 21284050
references: Nat Rev Mol Cell Biol. 2002 Sep;3(9):651-62
references: 12209125
references: Nat Protoc. 2007;2(2):329-33
references: 17406593
references: Cell Cycle. 2009 Jul 1;8(13):2005-13
references: 19550141
references: Clin Cancer Res. 2005 Mar 1;11(5):1815-20
references: 15756004
references: Annu Rev Immunol. 2005;23:1-21
references: 15771564
references: Cancer Res. 2006 Nov 1;66(21):10517-24
references: 17079474
references: Oncogene. 2003 Mar 13;22(10):1517-27
references: 12629515
references: Clin Cancer Res. 2003 Aug 1;9(8):3167-75
references: 12912969
references: Cancer Genomics Proteomics. 2007 Nov-Dec;4(6):387-98
references: 18204201
references: Lancet. 2001 Feb 17;357(9255):539-45
references: 11229684
references: Clin Cancer Res. 2010 Jan 1;16(1):77-87
references: 20028744
references: Cancer Metastasis Rev. 2009 Dec;28(3-4):335-44
references: 20012924
references: Oncol Rep. 2008 Apr;19(4):1007-13
references: 18357389
references: Nature. 2002 Dec 19-26;420(6917):860-7
references: 12490959
references: Cancer Cell. 2009 Apr 7;15(4):283-93
references: 19345327
references: Br J Cancer. 2005 Jun 20;92(12):2153-9
references: 15942628
references: Br J Cancer. 1995 Feb;71(2):354-6
references: 7841052
references: J Clin Invest. 2002 May;109(9):1139-42
references: 11994401
references: Int J Radiat Oncol Biol Phys. 2010 Mar 15;76(4):1214-24
references: 20206020