Expression profile of WNT molecules in prostate cancer and its regulation by aminobisphosphonates

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

Abstract

Skeletal metastases represent a frequent complication in patients with advanced prostate cancer (PCa) and often require bisphosphonate treatment to limit skeletal-related events. Metastasized PCa cells disturb bone remodeling. Since the WNT signaling pathway regulates bone remodeling and has been implicated in tumor progression and osteomimicry, we analyzed the WNT profile of primary PCa tissues and PCa cell lines and assessed its regulation by bisphosphonates. Prostate tissue (n = 18) was obtained from patients with benign prostate hyperplasia (BPH) and PCa patients with different disease stages. Serum samples were collected from 62 patients. Skeletal metastases were present in 17 patients of whom 6 had been treated with zoledronic acid. The WNT profile and its regulation by bisphoshonates were analyzed in tissue RNA extracts and serum samples as well as in osteotropic (PC3) and non-osteotropic (DU145, LNCaP) PCa cell lines. Several members of the WNT pathway, including WNT5A, FZD5, and DKK1 were highly up-regulated in PCa tissue from patients with advanced PCa. Interestingly, osteotropic cells showed a distinct WNT profile compared to non-osteotropic cells. While WNT5A, FZD5, and DKK1 were highly expressed in PC3 cells, WNT1 and SFRP1 mRNA levels were higher in DU145 cells. Moreover, zoledronic acid down-regulated mRNA levels of WNT5A (-34%), FZD5 (-60%), and DKK1 (-46%) in PC3 cells. Interestingly, patients with skeletal metastases who received zoledronic acid had twofold higher DKK1 serum levels compared to bisphosphonate-naive patients. The WNT signaling pathway is up-regulated in advanced PCa, differentially expressed in osteotropic versus non-osteotropic cells, and is regulated by zoledronic acid.

Details

Original languageEnglish
Pages (from-to)1593-1600
Number of pages8
JournalJournal of Cellular Biochemistry
Volume112
Issue number6
Publication statusPublished - Jun 2011
Peer-reviewedYes

External IDs

Scopus 79954461450
PubMed 21344486
researchoutputwizard legacy.publication#42799
researchoutputwizard legacy.publication#42419
researchoutputwizard legacy.publication#42470
ORCID /0000-0003-3717-3637/work/143072403
ORCID /0000-0002-8691-8423/work/143072935

Keywords

Sustainable Development Goals

Keywords

  • Aged, Blotting, Western, Bone Density Conservation Agents/therapeutic use, Cell Line, Tumor, Diphosphonates/pharmacology, Enzyme-Linked Immunosorbent Assay, Gene Expression Regulation, Neoplastic/drug effects, Humans, Imidazoles/therapeutic use, In Vitro Techniques, Intercellular Signaling Peptides and Proteins/genetics, Male, Middle Aged, Prostatic Neoplasms/drug therapy, Proto-Oncogene Proteins/genetics, Reverse Transcriptase Polymerase Chain Reaction, Wnt Proteins/genetics, Wnt-5a Protein, Wnt1 Protein/genetics, Wnt4 Protein, Zoledronic Acid