Volume 18, No 8, Aug 2008
ISSN: 1001-0602
EISSN: 1748-7838 2018
impact factor 17.848*
(Clarivate Analytics, 2019)
Volume 18 Issue 8, August 2008: 858-870
ORIGINAL ARTICLES
Receptor activator of NF-κB Ligand (RANKL) expression is associated with epithelial to mesenchymal transition in human prostate cancer cells
Valerie A Odero-Marah1, Ruoxiang Wang1, Gina Chu1, Majd Zayzafoon2, Jianchun Xu1, Chunmeng Shi1, Fray F Marshall1, Haiyen E Zhau1 and Leland WK Chung1
1Molecular Urology and Therapeutics Program, Department of Urology and Winship Cancer Institute, Emory University School of Medicine, 1365B Clifton Road, NE, Atlanta, GA 30322, USA;
2Department of Pathology, University of Alabamn, Birmingham, AL 35294
Correspondence: Haiyen E Zhau Leland WK Chung,(hzhau@emory.edu; lwchung@emory.edu )
Epithelial-mesenchymal transition (EMT) in cancer describes the phenotypic and behavioral changes of cancer cells from indolent to virulent forms with increased migratory, invasive and metastatic potential. EMT can be induced by soluble proteins like transforming growth factor β1 (TGFβ1) and transcription factors including Snail and Slug. We utilized the ARCaP
E/ARCaP
M prostate cancer progression model and LNCaP clones stably overexpressing Snail to identify novel markers associated with EMT. Compared to ARCaP
E cells, the highly tumorigenic mesenchymal ARCaP
M and ARCaP
M1 variant cells displayed a higher incidence of bone metastasis after intracardiac administration in SCID mice. ARCaP
M and ARCaP
M1 expressed mesenchymal stromal markers of vimentin and N-cadherin in addition to elevated levels of Receptor Activator of NF-κB Ligand (RANKL). We observed that both epidermal growth factor (EGF) plus TGFβ1 treatment and Snail overexpression induced EMT in ARCaP
E and LNCaP cells, and EMT was associated with increased expression of RANKL protein. Finally, we determined that the RANKL protein was functionally active, promoting osteoclastogenesis
in vitro. Our results indicate that RANKL is a novel marker for EMT during prostate cancer progression. RANKL may function as a link between EMT, bone turnover, and prostate cancer skeletal metastasis.
Cell Research (2008) 18:858-870. doi: 10.1038/cr.2008.84; published online 22 July 2008
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