Targeting estrogen/estrogen receptor alpha enhances Bacillus Calmette-Guérin efficacy in bladder cancer.
Recent studies showed the potential linkage of estrogen/estrogen receptor signaling with bladder tumorigenesis, yet detailed mechanisms remain elusive. Here we found a new potential therapy with the combination of Bacillus Calmette-Guerin (BCG) and the anti-estrogen ICI 182,780 led to better suppression of bladder cancer (BCa) than BCG alone. Mechanism dissection found ICI 182,780 could promote BCG attachment/internalization to the BCa cells through increased integrin-α5β1 expression and IL-6 release, which may enhance BCG-induced suppression of BCa cell growth via recruiting more monocytes/macrophages to BCa cells and increased TNF-α release. Consistently, in vivo studies found ICI 182,780 could potentiate the anti-BCa effects of BCG in the carcinogen-induced mouse BCa models. Together, these in vitro and in vivo results suggest that combining BCG with anti-estrogen may become a new therapeutic approach with better efficacy to suppress BCa progression and recurrence.
Chawnshang Chang Sex Hormone Research Center, Tianjin Institute of Urology, The 2nd Hospital of Tianjin Medical University, Tianjin, China.|George Whipple Lab for Cancer Research, Departments of Urology, Pathology and the Cancer Center, University of Rochester, Rochester, New York, United States of America.
Zhiqun
Z
Shang
Chawnshang Chang Sex Hormone Research Center, Tianjin Institute of Urology, The 2nd Hospital of Tianjin Medical University, Tianjin, China.
Yanjun
Y
Li
George Whipple Lab for Cancer Research, Departments of Urology, Pathology and the Cancer Center, University of Rochester, Rochester, New York, United States of America.
Iawen
I
Hsu
Chawnshang Chang Sex Hormone Research Center, Tianjin Institute of Urology, The 2nd Hospital of Tianjin Medical University, Tianjin, China.
Minghao
M
Zhang
Chawnshang Chang Sex Hormone Research Center, Tianjin Institute of Urology, The 2nd Hospital of Tianjin Medical University, Tianjin, China.|George Whipple Lab for Cancer Research, Departments of Urology, Pathology and the Cancer Center, University of Rochester, Rochester, New York, United States of America.
Jing
J
Tian
Chawnshang Chang Sex Hormone Research Center, Tianjin Institute of Urology, The 2nd Hospital of Tianjin Medical University, Tianjin, China.|George Whipple Lab for Cancer Research, Departments of Urology, Pathology and the Cancer Center, University of Rochester, Rochester, New York, United States of America.
Simeng
S
Wen
Chawnshang Chang Sex Hormone Research Center, Tianjin Institute of Urology, The 2nd Hospital of Tianjin Medical University, Tianjin, China.
Ruifa
R
Han
George Whipple Lab for Cancer Research, Departments of Urology, Pathology and the Cancer Center, University of Rochester, Rochester, New York, United States of America.
Edward M
EM
Messing
Chawnshang Chang Sex Hormone Research Center, Tianjin Institute of Urology, The 2nd Hospital of Tianjin Medical University, Tianjin, China.|George Whipple Lab for Cancer Research, Departments of Urology, Pathology and the Cancer Center, University of Rochester, Rochester, New York, United States of America.
Chawnshang
C
Chang
Chawnshang Chang Sex Hormone Research Center, Tianjin Institute of Urology, The 2nd Hospital of Tianjin Medical University, Tianjin, China.|George Whipple Lab for Cancer Research, Departments of Urology, Pathology and the Cancer Center, University of Rochester, Rochester, New York, United States of America.
Yuanjie
Y
Niu
Chawnshang Chang Sex Hormone Research Center, Tianjin Institute of Urology, The 2nd Hospital of Tianjin Medical University, Tianjin, China.|George Whipple Lab for Cancer Research, Departments of Urology, Pathology and the Cancer Center, University of Rochester, Rochester, New York, United States of America.
Shuyuan
S
Yeh
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001500:BCG Vaccine / Q000008:administration & dosage / Q000627:therapeutic use*; D002085:Butylhydroxybutylnitrosamine; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D004357:Drug Synergism; D004958:Estradiol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D065171:Estrogen Receptor Antagonists / Q000008:administration & dosage / Q000627:therapeutic use; D047628:Estrogen Receptor alpha / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005260:Female; D000077267:Fulvestrant; D006801:Humans; D039081:Integrin alpha5beta1 / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D009374:Neoplasms, Experimental / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism
D001500:BCG Vaccine; D065171:Estrogen Receptor Antagonists; D047628:Estrogen Receptor alpha; D039081:Integrin alpha5beta1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D000077267:Fulvestrant; D002085:Butylhydroxybutylnitrosamine; D004958:Estradiol
Bacillus Calmette-Guérin; bladder cancer; estrogen; estrogen receptor alpha