ArticlePloS one2017
Roles of VEGF-Flt-1 signaling in malignant behaviors of oral squamous cell carcinoma.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 25 citations in OpenAlex.
- IL-6 as a driver of bone invasion in IFIT2-depleted oral squamous cell carcinoma.Cancer immunology, immunotherapy : CII · 2026Article
- PlGF/Flt-1/MMP-1 axis in gingival carcinoma bone invasion.Histology and histopathology · 2025Article
- Anti- Cancer Potential of Diosgenin, a Steroidal Saponin, against Human Oral Cancer Cells.Asian Pacific journal of cancer prevention : APJCP · 2025Article
- The expression of salivary EGF, VEGF, endothelin, and transferrin in waterpipe and cigarette smokers.Odontology · 2025Observational
- Review
- Prognostic significance and relationship of SMAD3 phospho-isoforms and VEGFR-1 in gastric cancer: A clinicopathological study.World journal of gastrointestinal oncology · 2024Article
- Regulation of Tumor Vascular Microenvironment by Nestin and Fms-related Tyrosine Kinase 1 (FLT1) and Their Prognostic Significance in Renal Cell Carcinoma.Iranian journal of pathology · 2024Article
- A novel 3-miRNA network regulates tumour progression in oral squamous cell carcinoma.Biomarker research · 2023Article
- Identifying Drug Targets of Oral Squamous Cell Carcinoma through a Systems Biology Method and Genome-Wide Microarray Data for Drug Discovery by Deep Learning and Drug Design Specifications.International journal of molecular sciences · 2022Article
- Identification of the interleukin-8 (CXCL-8) pathway in feline oral squamous cell carcinoma - A pilot study.Canadian journal of veterinary research = Revue canadienne de recherche veterinaire · 2022Article
- Exploring the Mechanism ofEvidence-based complementary and alternative medicine : eCAM · 2021Article
- Intersecting Mechanisms of Hypoxia and Prostaglandin E2-Mediated Inflammation in the Comparative Biology of Oral Squamous Cell Carcinoma.Frontiers in oncology · 2021Review
- Association between excessive chronic iodine exposure and the occurrence of papillary thyroid carcinoma.Oncology letters · 2020Article
- Role of VEGFs/VEGFR-1 Signaling and its Inhibition in Modulating Tumor Invasion: Experimental Evidence in Different Metastatic Cancer Models.International journal of molecular sciences · 2020Review
- CCL28-induced RARβ expression inhibits oral squamous cell carcinoma bone invasion.The Journal of clinical investigation · 2019Article
- Thrombosis Risk Associated with Head and Neck Cancer: A Review.International journal of molecular sciences · 2019Review
- Immunohistochemically Detection of Angiogenesis in Oral Pre-Cancerous Lesions Compared with Oral Invasive CarcinomasAsian Pacific journal of cancer prevention : APJCP · 2018Article
- 3-O-Acetyloleanolic acid inhibits VEGF-A-induced lymphangiogenesis and lymph node metastasis in an oral cancer sentinel lymph node animal model.BMC cancer · 2018Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundVascular endothelial growth factor (VEGF) is a highly specific signaling protein for vascular endothelial cells that plays a critical role in tumor growth and invasion through angiogenesis, and may contribute to cell migration and activation of pre-osteoclasts, osteoclasts and some tumor cells.
objectivesWe aimed to clarify the detailed roles of VEGF-Flt-1 signaling in bone invasion of oral squamous cell carcinoma (OSCC) cells.
resultsForty-two (42) of 54 cases with gingival SCC (77.8%) strongly expressed VEGF, and had a significantly increased number of Flt-1+ osteoclasts (p<0.01) and more aggressive bone invasion (p<0.05). PlGF, a ligand of Flt-1, induced osteoclastogenesis in single culture of bone marrow cells (BMCs), and inhibition of Flt-1-signaling by VEGF tyrosine kinase inhibitor and It's down stream (Akt and ERK1/2) inhibitos reduced osteoclastogenesis in PlGF-stimulated BMCs (p<0.01). In molecular level, PlGF stimulation significantly upregulated RANKL expression in Flt-1-expressing HSC2 cells via phosphorylation of Akt and ERK1/2. In the co-culture of VEGF-producing HSC2 cells and BMCs, number of TRAP-positive osteoclasts markedly increased (p<0.01). The osteoclastogenesis was significantly inhibited by RANKL-neutralizing antibody (p<0.01) as well as by VEGF tyrosine kinase inhibitor (p<0.01) and it's downstream (Akt and ERK1/2) inhibitors (p<0.01, p<0.05, respectively).
conclusionVEGF-Flt-1 signaling induces osteoclastogenesis in OSCC through two possible ways: 1) VEGF produced from OSCC cells can directly stimulate the Flt-1 pathway in preosteoclasts to induce migration to future bone resorbing area and differentiation into osteoclasts, and 2) VEGF-Flt-1 signaling upregulates RANKL expression in OSCC cells, which indirectly leads to osteoclast differentiation. Therefore, blocking of the VEGF-Flt-1 signaling may help inhibit bone invasion of OSCC.
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