Infiltrated pre-adipocytes increase prostate cancer metastasis via modulation of the miR-301a/androgen receptor (AR)/TGF-β1/Smad/MMP9 signals.
High fat dietary intake may increase the risk of prostate cancer (PCa). Pre-adipocytes, one of the basic components in the tumor microenvironment (TME), are capable of differentiating into adipose tissues and play key roles to affect PCa progression. Here we found the pre-adipocytes could be recruited more easily to PCa than its surrounding normal prostate tissue. In vitro co-culture system also confirmed PCa has a better capacity than normal prostate to recruit pre-adipocytes. The consequences of recruiting more pre-adipocytes may then increase PCa cell invasion. Mechanism dissection revealed infiltrating pre-adipocytes might function through down-regulation of the androgen receptor (AR) via modulation of miR-301a, and then increase PCa cell invasion via induction of TGF-β1/Smad/MMP9 signals. The mouse model with orthotopically xenografted PCa CWR22Rv1 cells with pre-adipocytes also confirmed that infiltrating pre-adipocytes could increase PCa cell invasion via suppressing AR signaling. Together, our results reveal a new mechanism showing pre-adipocytes in the prostate TME can be recruited to PCa to increase PCa metastasis via modulation of the miR-301a/AR/TGF-β1/Smad/MMP9 signals. Targeting this newly identified signaling may help us to better inhibit PCa metastasis.
Sex Hormone Research Center, Department of Urology, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China.|George Whipple Lab for Cancer Research, Departments of Pathology and Urology, and The Wilmot Cancer Center, University of Rochester Medical Center, Rochester, New York, USA.
Hongjun
H
Xie
Sex Hormone Research Center, Department of Urology, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China.|George Whipple Lab for Cancer Research, Departments of Pathology and Urology, and The Wilmot Cancer Center, University of Rochester Medical Center, Rochester, New York, USA.
Lei
L
Li
Sex Hormone Research Center, Department of Urology, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China.|George Whipple Lab for Cancer Research, Departments of Pathology and Urology, and The Wilmot Cancer Center, University of Rochester Medical Center, Rochester, New York, USA.
Guodong
G
Zhu
Sex Hormone Research Center, Department of Urology, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China.|George Whipple Lab for Cancer Research, Departments of Pathology and Urology, and The Wilmot Cancer Center, University of Rochester Medical Center, Rochester, New York, USA.
Qiang
Q
Dang
Sex Hormone Research Center, Department of Urology, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China.
Zhenkun
Z
Ma
Sex Hormone Research Center, Department of Urology, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China.
Dalin
D
He
Sex Hormone Research Center, Department of Urology, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China.
Luke
L
Chang
Sex Hormone Research Center, Department of Urology, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China.|George Whipple Lab for Cancer Research, Departments of Pathology and Urology, and The Wilmot Cancer Center, University of Rochester Medical Center, Rochester, New York, USA.
Wenbing
W
Song
George Whipple Lab for Cancer Research, Departments of Pathology and Urology, and The Wilmot Cancer Center, University of Rochester Medical Center, Rochester, New York, USA.
Hong-Chiang
HC
Chang
Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, New York, USA.
John J
JJ
Krolewski
Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, New York, USA.
Kent L
KL
Nastiuk
George Whipple Lab for Cancer Research, Departments of Pathology and Urology, and The Wilmot Cancer Center, University of Rochester Medical Center, Rochester, New York, USA.
Shuyuan
S
Yeh
George Whipple Lab for Cancer Research, Departments of Pathology and Urology, and The Wilmot Cancer Center, University of Rochester Medical Center, Rochester, New York, USA.|Sex Hormone Research Center, China Medical University/Hospital, Taichung, Taiwan.
Chawnshang
C
Chang
D017667:Adipocytes / Q000473:pathology*; D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D018920:Coculture Techniques; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000473:pathology*; D009362:Neoplasm Metastasis; D011471:Prostatic Neoplasms / Q000473:pathology*; D060888:Real-Time Polymerase Chain Reaction; D011944:Receptors, Androgen / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D051785:Smad Proteins / Q000378:metabolism; D013234:Stem Cells / Q000473:pathology*; D014162:Transfection; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D059016:Tumor Microenvironment / Q000502:physiology*
C550735:MIRN301A microRNA, human; C573832:MIRN301 microRNA, mouse; D035683:MicroRNAs; D011944:Receptors, Androgen; D051785:Smad Proteins; D053773:Transforming Growth Factor beta1; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse
androgen receptor; mirna-301a; pre-adipocyte; prostate cancer