Infiltrated pre-adipocytes increase prostate cancer metastasis via modulation of the miR-301a/androgen receptor (AR)/ TGF-β1/Smad/MMP9 signals
Journal
Oncotarget
Journal Volume
6
Journal Issue
14
Pages
12326-12339
Date Issued
2015
Author(s)
Xie H.
Li L.
Zhu G.
Dang Q.
Ma Z.
He D.
Chang L.
Song W.
Krolewski J.J.
Nastiuk K.L.
Yeh S.
Chang C.
Abstract
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.
SDGs
Publisher
Impact Journals LLC
Type
journal article