ArticleMolecular cancer2011
Soluble vascular endothelial growth factor receptor-3 suppresses lymphangiogenesis and lymphatic metastasis in bladder cancer.
Article in Molecular cancer, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed, 116 citations in OpenAlex.
- Screening for potential targets to reduce stenosis in bioprosthetic heart valves.Scientific reports · 2021Trial
- Thrombospondin-4 drives lymphangiogenesis through cooperation with VEGF-C in human bladder cancer.International journal of medical sciences · 2026Article
- Bone Marrow Myeloid-Lymphatic Progenitors Expand Tumor Lymphatic Vasculature Through Cell Fusion.Cancers · 2025Article
- Integrating machine learning and genetic evidence to uncover novel gene biomarkers for colorectal cancer diagnosis.Discover oncology · 2025Article
- Vascular Endothelial Growth Factor C and D Signaling Pathways as Potential Targets for the Treatment of Neovascular Age-Related Macular Degeneration: A Narrative Review.Ophthalmology and therapy · 2024Review
- Analysis of the Genetic Characteristics and Metastatic Pathways of G1 and G2 Colorectal Neuroendocrine Neoplasms.Journal of the Endocrine Society · 2024Article
- Lymphatic vessel: origin, heterogeneity, biological functions, and therapeutic targets.Signal transduction and targeted therapy · 2024Review
- VEGFR-3 signaling in macrophages: friend or foe in disease?Frontiers in immunology · 2024Review
- Article
- Inflammation in Urological Malignancies: The Silent Killer.International journal of molecular sciences · 2023Review
- BANCR positively regulates the HIF-1α/VEGF-C/VEGFR-3 pathway in a hypoxic microenvironment to promote lymphangiogenesis in pancreatic cancer cells.Oncology letters · 2022Article
- Review
- Contemporary use trends and effect on survival of pelvic lymph node dissection for non-muscle-invasive bladder cancer.Frontiers in surgery · 2022Article
- Novel combinatorial strategies for boosting the efficacy of immune checkpoint inhibitors in advanced breast cancers.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2021Review
- Review
- SULF2 is a novel diagnostic and prognostic marker for high-grade bladder cancer with lymphatic metastasis.Annals of translational medicine · 2021Article
- Immune escape mechanisms and immunotherapy of urothelial bladder cancer.Journal of clinical and translational research · 2021Review
- [A Review of Celluar Senescence and Tumor Treatment].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2021Review
- Soluble Vegfr3 gene therapy suppresses multi-organ metastasis in a mouse mammary cancer model.Cancer science · 2020Article
- circNFIB1 inhibits lymphangiogenesis and lymphatic metastasis via the miR-486-5p/PIK3R1/VEGF-C axis in pancreatic cancer.Molecular cancer · 2020Article
1 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 5 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMost bladder cancer patients experience lymphatic metastasis in the course of disease progression, yet the relationship between lymphangiogenesis and lymphatic metastasis is not well known. The aim of this study is to elucidate underlying mechanisms of how expanded lymphatic vessels and tumor microenvironment interacts each other and to find effective therapeutic options to inhibit lymphatic metastasis.
resultsThe orthotopic urinary bladder cancer (OUBC) model was generated by intravesical injection of MBT-2 cell lines. We investigated the angiogenesis, lymphangiogenesis, and CD11b+/CD68+ tumor-associated macrophages (TAM) by using immunofluorescence staining. OUBC displayed a profound lymphangiogenesis and massive infiltration of TAM in primary tumor and lymphatic metastasis in lymph nodes. TAM flocked near lymphatic vessels and express higher levels of VEGF-C/D than CD11b- cells. Because VEGFR-3 was highly expressed in lymphatic vascular endothelial cells, TAM could assist lymphangiogenesis by paracrine manner in bladder tumor. VEGFR-3 expressing adenovirus was administered to block VEGF-C/D signaling pathway and clodronate liposome was used to deplete TAM. The blockade of VEGF-C/D with soluble VEGF receptor-3 markedly inhibited lymphangiogenesis and lymphatic metastasis in OUBC. In addition, the depletion of TAM with clodronate liposome exerted similar effects on OUBC.
conclusionVEGF-C/D are the main factors of lymphangiogenesis and lymphatic metastasis in bladder cancer. Moreover, TAM plays an important role in these processes by producing VEGF-C/D. The inhibition of lymphangiogenesis could provide another therapeutic target to inhibit lymphatic metastasis and recurrence in patients with invasive bladder cancer.
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