ArticlePloS one2015
Primary Tumor-Secreted Lymphangiogenic Factors Induce Pre-Metastatic Lymphvascular Niche Formation at Sentinel Lymph Nodes in Oral Squamous Cell Carcinoma.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 57 citations in OpenAlex.
- Predictive factors for false negatives following sentinel lymph node biopsy in early oral cavity cancer.Scientific reports · 2022Trial
- Unraveling the impact of cancer-associated fibroblasts on lymphatic metastasis of head and neck squamous cell carcinoma.Cellular oncology (Dordrecht, Netherlands) · 2025Review
- VEGFD/VEGFR2 axis induces the dedifferentiation of high endothelial venules and impairs lymphocyte homing.JCI insight · 2025Article
- The Tight Relationship Between the Tumoral Microenvironment and Radium-223.Biomedicines · 2025Review
- Exploratory spatial transcriptomic profiling of peritumoral Th2 immune polarization in HPV-positive oropharyngeal cancer.Frontiers in oncology · 2025Article
- Ischemic stroke of undetermined source as a priming event for brain metastasis: a case report and systematic literature review.Frontiers in oncology · 2025Article
- Article
- Review
- Cross‑talk between lymphangiogenesis and malignant melanoma cells: New opinions on tumour drainage and immunization (Review).Oncology letters · 2024Review
- Small extracellular vesicles promote the formation of the pre-metastatic niche through multiple mechanisms in colorectal cancer.Cell cycle (Georgetown, Tex.) · 2024Review
- Article
- Article
- Premetastatic Niche: A Novel Area for Research in Metastasis with a Potential as Therapeutic Targeting in Oral Cancer.Journal of pharmacy & bioallied sciences · 2023Review
- Evaluation of premetastatic changes in lymph nodes(pN0) of oral tongue tumour: A prospective observational Study.F1000Research · 2023Observational
- Review
- Periostin in lymph node pre-metastatic niches governs lymphatic endothelial cell functions and metastatic colonization.Cellular and molecular life sciences : CMLS · 2022Article
- The Regulation of Lymph Node Pre-Metastatic Niche Formation in Head and Neck Squamous Cell Carcinoma.Frontiers in oncology · 2022Review
- Opposing Roles of Vascular Endothelial Growth Factor C in Metastatic Dissemination and Resistance to Radio/Chemotherapy: Discussion of Mechanisms and Therapeutic Strategies.Methods in molecular biology (Clifton, N.J.) · 2022Review
- Liquid Biopsy in Pre-Metastatic Niche: From Molecular Mechanism to Clinical Application.Frontiers in immunology · 2022Review
- The pre-metastatic niche in lymph nodes: formation and characteristics.Cellular and molecular life sciences : CMLS · 2021Review
Corrections and comments
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Authors and funding
10 authors at 7 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivesThe objectives of this study were to evaluate the formation of lymphvascular niches in lymph nodes of patients with oral squamous cell carcinoma (OSCC), and investigate the roles of lymphangiogenic and angiogenic factors, such as vascular endothelial growth factor (VEGF)-A, VEGF-C, and VEGF-D, expressed in the primary tumors. MATERIALS AND
methodsForty-four patients with previously untreated clinically late T2 or T3 OSCC of cN0 were evaluated for primary tumors and 166 sentinel lymph nodes (SLNs). Primary tumors were immunohistochemically analyzed for expressions of VEGFs. Densities of lymphatic vessels (LVDpodoplanin) and high endothelial venules (HEVD) in the SLNs were also calculated using antibodies for each marker, podoplanin and MECA-79, respectively.
resultsIn 25 patients, all lymph nodes were metastasis-negative, whereas, in 19 patients, metastasis was positive for at least one lymph node (either at SLN, non-SLN, or nodal recurrence). From the analyses of 140 SLNs without metastasis, LVDpodoplanin in 50 SLNs of metastasis-positive cases was significantly higher than that in 90 SLNs of metastasis-negative cases (p = 0.0025). HEVD was not associated with lymph node metastasis. The patients with VEGF-A-High or VEGF-D-High tumors had significantly higher LVDpodoplanin than patients with their Low counterparts (p = 0.0233 and p = 0.0209, respectively). In cases with lymph node metastasis, the VEGF-D-expression score was significantly higher than in those without lymph node metastasis (p = 0.0006).
conclusionsThese results suggest that lymph node lymphangiogenesis occurs before metastasis in OSCC. VEGF-A and VEGF-D play critical roles in this process. VEGF-D is a potential predictive marker of positive lymph node metastasis in cN0 patients.
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