ArticleJournal of translational medicine2025
The CTSZ-TRA2A-IL32 axis defines a targetable macrophage-dependent pathway in metastatic prostate cancer.
Article in Journal of translational medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
8 citing papers in PubMed.
- Integrin-mediated mechanotransduction in the tumor microenvironment: macrophage-centered signaling mechanisms and immune remodeling.Journal of translational medicine · 2026Review
- Macrophage-derived CTSZ promotes prostate cancer progression via αVβ3 integrin-mediated activation of the AKT/FOXO1/JUNB signaling axis.Cancer cell international · 2026Article
- VCAN promotes the progression and recurrence of esophageal squamous cell carcinoma by remodeling the tumor microenvironment.Scientific reports · 2026Article
- Cathepsins in prostate cancer: multifunctional regulators in tumor progression and therapeutic prospects-a narrative review.Translational andrology and urology · 2026Review
- Comparative Blood-Based Transcriptomic Profiles of Prostate Cancer Patients from South Africa and the USA: A Cross-Sectional Pilot Study.Journal of Cancer · 2026Article
- Inflammasome-associated pyroptosis and tumor angiogenesis in prostate cancer.Iranian journal of basic medical sciences · 2026Review
- Revisiting the impact of cathepsin Z in prostate cancer: concerns and insights.Journal of translational medicine · 2025Article
- Alternative Splicing: A Critical Regulator in Human Bone Biology and Tumor Progression.Research (Washington, D.C.) · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors.
Funding
Abstract
backgroundEmerging evidence underscores the pivotal role of M2-polarized tumor-associated macrophages (M2-TAMs) in orchestrating immunosuppressive tumor microenvironments that fuel metastatic dissemination in prostate cancer (PCa), yet the fundamental mechanisms governing M2-TAM trafficking in lethal PCa progression remain poorly understood.
methodsMulti-cohort transcriptomic analyses were performed to identify metastasis-associated genes, with CTSZ prioritized as a key cathepsin linked to prostate cancer progression. Circulating tumor and bone metastatic mouse models were employed to investigate CTSZ-driven M2-TAM infiltration and metastatic behavior. Mechanistic studies included proteasomal degradation assays, IL32 pre-mRNA splicing analysis, and IL-32 binding experiments using RGD motif-dependent interactions. Therapeutic efficacy was tested with the ITGA5 inhibitor GLPG0187 in preclinical models.
resultsElevated CTSZ expression shows strong clinical association with advanced pathological progression. CTSZ overexpression in PCa cells drives lung metastasis dissemination and bone metastatic in vivo model but fails to enhance cell-intrinsic oncogenic behaviors in vitro systems. Overexpression of CTSZ promotes M2-TAM infiltration and metastasis by inducing TRA2A degradation via the proteasome pathway, which alleviates TRA2A-mediated suppression of IL32 alternative splicing. Enhanced IL-32 secretion facilitates M2-TAM recruitment through binding to macrophage integrin ITGA5. Pharmacological inhibition of ITGA5 with GLPG0187 significantly reduced metastatic burden and M2-TAM infiltration in vivo.
conclusionsThe CTSZ/TRA2A/IL-32/ITGA5 axis orchestrates protumoral immunity in PCa metastasis by driving M2-TAM recruitment. Targeting this pathway, particularly through ITGA5 blockade, represents a promising therapeutic strategy to inhibit metastatic progression and remodel the immunosuppressive tumor microenvironment.
Indexed as
Identifiers
What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.