ArticleBiomarker research2024
GDF15 propeptide promotes bone metastasis of castration-resistant prostate cancer by augmenting the bone microenvironment.
Article in Biomarker research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed.
- Exploring the molecular mechanism of benzo[a]pyrene affecting prostate cancer based on network toxicology and external validation.Molecular diversity · 2026Article
- Clinical implications of serum GDF15 propeptide as a biomarker for bone metastasis across common solid tumors: a real-world multi-institutional study.Biomarker research · 2026Article
- Osteocyte-Derived GDF15 Promotes Paclitaxel Resistance, Tumor Growth, and Bone Microenvironment Regulation in Prostate Cancer.Current issues in molecular biology · 2026Article
- High RMI1 expression is associated with cancer cell progression and poor prognosis in prostate cancer.Oncology reports · 2026Article
- A Hypoxia and Immune Escape-Related Gene Signature for the Diagnosis of Prostate Cancer: An Integrated Bioinformatics Study.International journal of medical sciences · 2026Article
- Interplay of IL-6, GDF-15 and Sarcopenia in Patients With Bladder Cancer Undergoing Radical Cystectomy and Its Implications on Survival.Journal of cachexia, sarcopenia and muscle · 2025Article
- Distinct osteoclastogenic potential of granulocyte-macrophage colony-stimulating factor-induced monocyte subsets.Bone reports · 2025Article
- The Multifaceted Role of Growth Differentiation Factor 15 (GDF15): A Narrative Review from Cancer Cachexia to Target Therapy.Biomedicines · 2025Review
- NAG-1/GDF15 as a tumor suppressor in colorectal cancer: inhibition of β-catenin and NF-κB pathways via interaction with EpCAM.Cell death & disease · 2025Article
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20 authors.
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Abstract
backgroundBone metastasis (BM) is a common and fatal condition in patients with castration-resistant prostate cancer (CRPC). However, there are no useful blood biomarkers for CRPC with BM, and the mechanism underlying BM is unclear. In this study, we investigated precise blood biomarkers for evaluating BM that can improve the prognosis of patients with CRPC.
methodsWe comprehensively examined culture supernatants from four prostate cancer (PCa) cell lines using Orbitrap mass spectrometry to identify specific proteins secreted abundantly by PCa cells. The effects of this protein to PCa cells, osteoblasts, osteoclasts were examined, and BM mouse model. In addition, we measured the plasma concentration of this protein in CRPC patients for whom bone scan index (BSI) by bone scintigraphy was performed.
resultsA total of 2,787 proteins were identified by secretome analysis. We focused on GDF15 propeptide (GDPP), which is secreted by osteoblasts, osteoclasts, and PCa cells. GDPP promoted the proliferation, invasion, and migration of PC3 and DU145 CRPC cells, and GDPP aggravated BM in a mouse model. Importantly, GDPP accelerated bone formation and absorption in the bone microenvironment by enhancing the proliferation of osteoblasts and osteoclasts by upregulating individual transcription factors such as RUNX2, OSX, ATF4, NFATc1, and DC-STAMP. In clinical settings, including a total of 416 patients, GDPP was more diagnostic of BM than prostate-specific antigen (PSA) (AUC = 0.92 and 0.78) and the seven other blood biomarkers (alkaline phosphatase, lactate dehydrogenase, bone alkaline phosphatase, tartrate-resistant acid phosphatase 5b, osteocalcin, procollagen I N-terminal propeptide and mature GDF15) in patients with CRPC. The changes in BSI over time with systemic treatment were correlated with that of GDPP (r = 0.63) but not with that of PSA (r = -0.16).
conclusionsGDPP augments the tumor microenvironment of BM and is a novel blood biomarker of BM in CRPC, which could lead to early treatment interventions in patients with CRPC.
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