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2000
Volume 32, Issue 5
  • ISSN: 0929-8665
  • E-ISSN: 1875-5305

Abstract

Background and Objective

Canonical Wnt (Wnt/β-catenin) signaling maintains bone homeostasis by promoting osteoblastic activities. The inhibitory factor, Dickkopf-1 (DKK1), enhances bone resorption in malignant diseases. Low-density lipoprotein-related protein (LRP) 5 is antagonized by DKK1. This study aimed to investigate the expression of DKK1 and LRP5 in renal cell carcinoma bone metastasis (RCC-BM).

Methods

RCC-BM patients with paired samples of primary and metastatic lesions were selected for the study (RCC-BM group). RCC patients without any metastasis served as the control group (RCC-only group). Immunohistochemical staining with monoclonal anti-DKK1 and polyclonal anti-LRP5 antibody was conducted on paraffin-embedded slides. The staining results were recorded using scoring according to staining intensity in the renal tissue adjacent to the tumor, primary RCC lesions, and RCC-BM lesions.

Results

DKK1 was differently expressed among normal renal tissues, primary RCC, and RCC-BM tissues (0.001). The DKK1 expression in primary RCC was significantly lower than that in normal renal tissues (0.001) without a difference between the RCC-BM and RCC-only groups. DKK1 expression in bone metastasis was significantly higher than that in primary tumors (0.001). For RCC-BM patients, the expression of LRP5 in the primary tumor was significantly lower than that in adjacent renal tissues (0.01). The tendency of lower expression was found in primary RCC from RCC-BM patients compared to RCC without metastasis (=0.073).

Conclusion

A “rebound” pattern of DKK1 expression in bone metastasis lesions and the decreasing LRP5 expression in primary lesions of RCC-BM patients suggested that Wnt/β-catenin signaling was inhibited in RCC-BM. The overexpression of DKK1 and reduced expression of LRP5 suggest that these markers may be useful for the early prediction of RCC-BM.

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2025-05-07
2025-10-25

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Inhibition of Canonical Wnt Signaling in Renal Cell Carcinoma Bone Metastasis: An Immunohistochemical Analysis of DKK1 and LRP5 Expression
PPL 32, 327 (2025); https://doi.org/10.2174/0109298665357331250416081850
/content/journals/ppl/10.2174/0109298665357331250416081850
/content/journals/ppl/10.2174/0109298665357331250416081850
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  • Article Type:     Research Article
Keyword(s): bone metastasis; Dickkopf-1; low-density lipoprotein related receptor protein 5; Renal cell carcinoma; tyrosine kinase inhibitors; Wnt/β-catenin signaling

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