Polish Journal of Pathology
eISSN: 2084-9869
ISSN: 1233-9687
Polish Journal of Pathology
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without publication fees
1/2025
vol. 76
 
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abstract:
Original paper

Crosstalk between OPG/RANKL/RANK in bone marrow mesenchymal stem cells and Wnt/b-catenin pathway in prostate cancer cells regulates bone metastasis of prostate cancer

Shihua Ye
1
,
Qiongyun Lin
1
,
Meihua Deng
1
,
Shulong Huang
1
,
Changlin Mao
1
,
Jiabin Zhang
1
,
Wuming Zhan
1
,
Guangbing Chen
1

  1. Department of Urology, Mindong Hospital Affiliated to Fujian Medical University, Fuan City, Ninde, Fujian, 355000, China
Pol J Pathol 2025; 76 (1): 25-37
DOI: https://doi.org/10.5114/pjp.2025.150029
Online publish date: 2025/04/28
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This study aimed to investigate whether the crosstalk between the osteoprotegerin (OPG)/receptor activator of nuclear factor-kB (RANK)/receptor activator of nuclear factor-kB ligand (RANKL) in bone marrow mesenchymal stem cells (BMSCs) and Wnt/b-catenin pathways in Pca cells regulates bone metastasis of PCa.

Our study showed that there was increased OPG/RANKL/RANK and b-catenin expression in the tissue of PCa and its bone metastasis. This study further showed that RANKL knockdown in BMSCs or b-catenin knockdown in PC-3s blocked the proliferation and migration of BMSCs and the proliferation, migration, and invasion of PC-3s in vitro. Conversely, RANKL overexpression in BMSCs and b-catenin overexpression in PC-3s promoted the proliferation and migration of BMSCs and the proliferation, migration, and invasion of PC-3s in vitro. These data indicate that the RANKL pathway in BMSCs promoted the PC-3s invasion and the catenin pathway in PC-3s activated BMSCs with expression of cancer-associated fibroblast markers, which promoted the bone metastasis.

This suggests that the interaction and crosstalk between BMSCs in bone microenvironment and PCa play a critical role in the exquisite tropism for Pca bone metastasis. Cancer therapies classically target tumour cells; however, based on this study, targeting BMSCs in bone microenvironment is a reasonable option for PCa therapy strategy.
keywords:

OPG/RANKL/RANK, bone marrow mesenchymal stem cell, Wnt/b-catenin, prostate cancer, bone metastasis
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