Bone remodeling: a central mechanism in prostate cancer bone metastasis
Abstract
Prostate cancer (PCa) commonly metastasizes to bone, leading predominantly to osteoblastic lesions driven by intricate cellular interactions within the bone microenvironment. While osteoclasts (OCLs) initiate bone remodeling through resorption, their contribution to PCa progression appears limited, as pharmacological inhibition with bisphosphonates and RANKL antagonists yields only modest clinical benefit. In contrast, osteoblasts (OBs) exert dual roles, either promoting or restraining tumor growth through context-dependent signaling pathways, including Wnt5a-mediated dormancy and transforming growth factor-beta (TGF-β)-induced epithelial-mesenchymal transition (EMT). Bone-derived growth factors such as insulin-like growth factor I/II (IGF-I/II), fibroblast growth factor 23 (FGF-23), and platelet-derived growth factor (PDGF) further enhance tumor colonization. Osteocytes (OCYs), the most abundant and long-lived bone cells, directly interact with PCa cells and, in response to altered mechanotransduction, release pro-metastatic mediators including CCL5 and matrix metalloproteinases (MMPs). Moreover, PCa cells actively reprogram the bone niche by secreting exosomes and paracrine factors such as parathyroid hormone-related peptide (PTHrP) and Wnt7b, driving OBs and OCYs toward tumor-supportive phenotypes. Together, these reciprocal interactions establish a self-reinforcing cycle of bone remodeling and tumor progression. This review underscores the central role of bone remodeling…
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