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Alterations of the RANKL pathway in blood and bone marrow samples of prostate cancer patients without bone metastases.
MedLine Citation:
PMID:  22715006     Owner:  NLM     Status:  Publisher    
OBJECTIVES: The receptor activator of the NF-kB ligand (RANKL) pathway is a key mediator of prostate cancer (PC)-induced bone disease. However, little is known about this pathway in patients with non-metastatic PC. We aimed to investigate whether changes of RANKL, its inhibitor osteoprotegerin (OPG) and bone marrow-mesenchymal stromal cells (BM-MSCs) occur in PC patients without manifest bone metastases. PATIENTS AND METHODS: We determined OPG and soluble RANKL (sRANKL) in serum and corresponding bone marrow (BM) samples of 140 patients before radical prostatectomy by enzyme-linked immunosorbent assay (ELISA). As control serum samples of 50 patients with benign prostate hyperplasia were analyzed. BM mononuclear cells (BMNCs) of 16 PC patients were analyzed for expression of RANKL and CD271 (as marker for MSCs) by flow cytometry. RESULTS: PC patients had significantly lower serum levels of OPG compared to BPH patients (P = 0.007), whereas no differences were observed for serum sRANKL (P = 0.74). Both OPG and sRANKL concentrations of serum and corresponding BM samples correlated significantly (P < 0.0001 each). Interestingly, in PC patients, lower serum and BM OPG levels were associated with a higher proportion of BM-MSCs (P = 0.04 and 0.0016, respectively). No correlations were observed for sRANKL, OPG, BM-MSCs, and established risk parameters of PC. DISCUSSION: The results of the study indicate that localized PC is associated with early specific changes of the RANKL pathway in serum and bone marrow (BM). These changes might be part of the pre-metastatic niche of PC and implicate a potential benefit of RANKL inhibition in patients with localized PC. Prostate © 2012 Wiley Periodicals, Inc.
Tilman Todenhöfer; Jörg Hennenlotter; Benjamin Joachim Schmiedel; Andrea Hohneder; Sabrina Grimm; Ursula Kühs; Helmut Rainer Salih; Hans-Jörg Bühring; Tanja Fehm; Georgios Gakis; Gunnar Blumenstock; Stefan Aufderklamm; David Schilling; Arnulf Stenzl; Christian Schwentner
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-6-19
Journal Detail:
Title:  The Prostate     Volume:  -     ISSN:  1097-0045     ISO Abbreviation:  -     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-6-20     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8101368     Medline TA:  Prostate     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012 Wiley Periodicals, Inc.
Department of Urology, University Hospital Tuebingen, Tuebingen, Germany.
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