ArticleThe Journal of clinical investigation2012
RhoGDI2 suppresses lung metastasis in mice by reducing tumor versican expression and macrophage infiltration.
Article in The Journal of clinical investigation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 papers.
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Who cites it
99 citing papers in PubMed, 135 citations in OpenAlex.
- GDI2 protein: research progress and its mechanisms in diseases.Frontiers in cell and developmental biology · 2026Review
- ARHGDIB as a prognostic biomarker and modulator of the immunosuppressive microenvironment in glioma.Cancer immunology, immunotherapy : CII · 2025Article
- Regulation of versican expression in macrophages is mediated by canonical type I interferon signaling via ISGF3.American journal of physiology. Cell physiology · 2024Article
- Construction and assessment of an angiogenesis-related gene signature for prognosis of head and neck squamous cell carcinoma.Discover oncology · 2024Article
- CD44 in Bladder Cancer.Cancers · 2024Review
- Regulation of Versican Expression in Macrophages is Mediated by Canonical Type I Interferon Signaling via ISGF3.bioRxiv : the preprint server for biology · 2024Article
- The Novel Role of GDI2: A Mini-Review.Annals of medicine and medical research · 2024Article
- Article
- New insights into the correlations between circulating tumor cells and target organ metastasis.Signal transduction and targeted therapy · 2023Review
- Metastasis suppressor genes and their role in the tumor microenvironment.Cancer metastasis reviews · 2023Review
- Bladder cancer.Nature reviews. Disease primers · 2023Review
- A diagnostic model for sepsis-induced acute lung injury using a consensus machine learning approach and its therapeutic implications.Journal of translational medicine · 2023Article
- Differential functions of RhoGDIβ in malignant transformation and progression of urothelial cell following N-butyl-N-(4-hydmoxybutyl) nitrosamine exposure.BMC biology · 2023Article
- Non-muscle-invasive bladder cancer molecular subtypes predict differential response to intravesical Bacillus Calmette-Guérin.Science translational medicine · 2023Article
- VCAN Hypomethylation and Expression as Predictive Biomarkers of Drug Sensitivity in Upper Urinary Tract Urothelial Carcinoma.International journal of molecular sciences · 2023Article
- Anti-inflammatory role of extracellular l-arginine through calcium sensing receptor in human renal proximal tubular epithelial (HK-2) cells.International immunopharmacology · 2023Article
- Matrix proteoglycans in tumor inflammation and immunity.American journal of physiology. Cell physiology · 2022Review
- The dynamic roles of the bladder tumour microenvironment.Nature reviews. Urology · 2022Review
- Review
- Article
39 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
Abstract
Half of patients with muscle-invasive bladder cancer develop metastatic disease, and this is responsible for most of the deaths from this cancer. Low expression of RhoGTP dissociation inhibitor 2 (RhoGDI2; also known as ARHGDIB and Ly-GDI) is associated with metastatic disease in patients with muscle-invasive bladder cancer. Moreover, a reduction in metastasis is observed upon reexpression of RhoGDI2 in xenograft models of metastatic cancer. Here, we show that RhoGDI2 suppresses lung metastasis in mouse models by reducing the expression of isoforms V1 and V3 of the proteoglycan versican (VCAN; also known as chondroitin sulfate proteoglycan 2 [CSPG2]). In addition, we found that high versican levels portended poor prognosis in patients with bladder cancer. The functional importance of tumor expression of versican in promoting metastasis was established in in vitro and in vivo studies in mice that implicated a role for the chemokine CCL2 (also known as MCP1) and macrophages. Further analysis indicated that RhoGDI2 suppressed metastasis by altering inflammation in the tumor microenvironment. In summary, we demonstrate what we believe to be a new mechanism of metastasis suppression that works by reducing host responses that promote metastatic colonization of the lung. Therapeutic targeting of these interactions may provide a novel adjuvant strategy for delaying the appearance of clinical metastasis in patients.
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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 OpenQuestion graph.