Estrogen represses hepatocellular carcinoma (HCC) growth via inhibiting alternative activation of tumor-associated macrophages (TAMs).
BACKGROUND
Hepatocarcinoma cancer (HCC) occurs more often in men than in women, and little is known about its underlying molecular mechanisms.


RESULTS
We identify that 17β-estradiol (E2) could suppress tumor growth via regulating the polarization of macrophages.


CONCLUSIONS
Estrogen functions as a suppressor for macrophage alternative activation.


CONCLUSIONS
These studies introduce a novel mechanism for suppressing male-predominant HCC. Hepatocarcinoma cancer (HCC), one of the most malignant cancers, occurs significantly more often in men than in women; however, little is known about its underlying molecular mechanisms. Here we identified that 17β-estradiol (E2) could suppress tumor growth via regulating the polarization of macrophages. We showed that E2 re-administration reduced tumor growth in orthotopic and ectopic mice HCC models. E2 functioned as a suppressor for macrophage alternative activation and tumor progression by keeping estrogen receptor β (ERβ) away from interacting with ATP5J (also known as ATPase-coupling factor 6), a part of ATPase, thus inhibiting the JAK1-STAT6 signaling pathway. These studies introduce a novel mechanism for suppressing male-predominant HCC.
State Key Laboratory of Pharmaceutical Biotechnology and Model Animal Research Center, Nanjing University, Nanjing 210093, China.
Weiwei
W
Yang
Yan
Y
Lu
Yichen
Y
Xu
Lizhi
L
Xu
Wei
W
Zheng
Yuanyuan
Y
Wu
Long
L
Li
Pingping
P
Shen
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000276:immunology* / Q000503:physiopathology; D002460:Cell Line; D049109:Cell Proliferation; D002478:Cells, Cultured; D015536:Down-Regulation; D047629:Estrogen Receptor beta / Q000235:genetics / Q000276:immunology; D004967:Estrogens / Q000276:immunology*; D005260:Female; D006801:Humans; D053613:Janus Kinase 1 / Q000235:genetics / Q000276:immunology; D008113:Liver Neoplasms / Q000235:genetics / Q000276:immunology* / Q000503:physiopathology; D008262:Macrophage Activation; D008264:Macrophages / Q000166:cytology / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D050800:STAT6 Transcription Factor / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction
D047629:Estrogen Receptor beta; D004967:Estrogens; D050800:STAT6 Transcription Factor; C507905:Jak1 protein, mouse; D053613:Janus Kinase 1