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Growth factor active in angiogenesis, and endothelial cell growth, stimulating their proliferation and migration and also has effects on the permeability of blood vessels. May function in angiogenesis of the venous and lymphatic vascular systems during embryogenesis, and also in the maintenance of differentiated lymphatic endothelium in adults. Binds and activates KDR/VEGFR2 and FLT4/VEGFR3 receptors.
Gene References into Functions
A possible mechanism has been proposed of the TGF-beta-VEGF-C pathway in which TGF-beta promotes VEGF-C production in tubular epithelial cells, macrophages, and mesothelial cells, leading to lymphangiogenesis in renal and peritoneal fibrosis. (Review) PMID: 30142879
The mutation induced skipping of exon 2 of VEGFC resulting in a frameshift and the introduction of a premature stop codon (p.Ala50ValfsTer18). The mutation leads to a loss of the entire VEGF-homology domain and the C-terminus. PMID: 30071673
VEGFR-3 and CAV3 expression demonstrated immunohistochemically in SMCs of the tunica media of SV grafts predicted their early restenosis in triple-vessel CAD patients. CAV2 protein expression in SMCs of ITA grafts indicated the risk of early graft failure both in double-vessel and triple-vessel CAD subjects. PMID: 29557990
VEGF-C expression and secretion in gastric cancer is downregulated by kallistatin. PMID: 29243194
Concomitant high expression of survivin and VEGF-C is closely associated with LNM status of PTC patients, which suggests their cooperation in the metastatic process. PMID: 29578160
TNFSF15, a cytokine mainly produced by blood endothelial cells, facilitates tumor lymphangiogenesis by upregulating VEGFC expression in A549 cells. PMID: 29890027
serum levels not elevated in patients with erythrodermic mycosis fungoides/Sezary syndrome PMID: 28925057
SPARC expression was inversely associated with the degree of malignancy and it had a negative correlation with VEGF-C and VEGF-D expression. Results suggest SPARC might function as a tumor suppressor inhibiting angiogenesis and lymphangiogenesis in ovarian cancer by reducing the expression of VEGF-C and VEGF-D. PMID: 29075785
VEGF-A/VEGF-C analysis showed higher positivity in metastatic nodes and higher positivity in the surrounding negative nodes from positive cases in comparison with nonmetastatic patients. PMID: 28984690
this study shows that decidual NK cells facilitate the interaction between trophoblastic and endothelial cells via VEGF-C and HGF PMID: 28653669
Lymphangiogenesis during tubulointerstitial fibrosis to be associated with increased expression of CTGF and VEGF-C in human obstructed nephropathy as well as in diabetic kidney disease. vitro, CTGF induced VEGF-C production in HK-2 cells, while CTGF siRNA suppressed transforming growth factor beta1-induced VEGF-C upregulation. PMID: 28545716
study is the first to describe the mechanism of leptin-promoted lymphangiogenesis by upregulating VEGF-C expression in chondrosarcomas. PMID: 27345723
Retroperitoneal tumour progression in EOC patients is associated with high VEGF-C expression. PMID: 28591727
Mechanistic investigations indicated that BDNF facilitated VEGF-C-dependent lymphangiogenesis through the MEK/ERK/mTOR signaling pathway. PMID: 28771226
Results has shown that VEGF-C was highly expressed in non-small cell lung cancer (NSCLC) tissues and metastatic lymph nodes. VEGF-C expression levels was significantly correlated with lymph node metastasis in NSCLC. Along with CXCR4, VEGF-C might synergically promote lymphatic metastasis in lung cancer and might be a clinical predictor of lymph node metastasis in NSCLC patients. PMID: 28925100
CXCR4, CCR7, VEGF-C and VEGF-D expression might have synergistic effects on the lymph node metastasis in patients with cervical cancer. PMID: 28535405
prolactin induction of VEGF-C and Runx2 was inhibited partly by Carboxypeptidase-D inhibitors, implicating nitric oxide , produced by PRL-regulated Carboxypeptidase-D, in breast cancer progression PMID: 28364216
Study is the first to describe the mechanism of bFGF-promoted lymphangiogenesis by upregulating VEGF-C expression in chondrosarcomas. PMID: 27229532
eIF4E promoted cholangiocarcinoma cell metastasis by up-regulating the expression of VEGF-C, MMP-2 and suppressing E-cadherin expression. PMID: 27907907
High expression of VEGF-C in the primary tumour may be a good determinant for detection of occult tumour cells in the lymph nodes of OSCC cases. PMID: 27417330
document for the first time that CCL5 induces tumor lymphangiogenesis by the induction of VEGF-C in human cancer cells. PMID: 27166194
Data suggest that the BRG1/STAT3/VEGFC in tumor-associated lymphangiogenesis might lead to the discovery of novel therapeutic targets in the treatment of cancers with BRG1 loss of function. PMID: 27145366
Studied the effect of recombinant human vascular endothelial growth factor (VEGF)-C on lymphangiogenesis, inflammation, and fibrosis in the mouse kidney using the unilateral ureteral obstruction (UUO); lymphangiogenesis was significantly induced in the UUO+VEGF-C group. In lymphatic endothelial cells, VEGF-C increased the activity and proliferation of such cells and expression of VCAM-1. PMID: 29083411
This study reports that human dendritic cells produce VEGF-C, a cytokine with potent pro-lymphangiogenic activity when stimulated with IFN-gamma PMID: 26987844
Association of coexpressed high levels of VEGF-C and active MMP-9 with lymphatic spreading and local invasiveness of Papillary thyroid carcinoma (PTC) suggests their potential usefulness as predictive biomarkers of aggressive PTC behavior. PMID: 27806941
Data show that VEGF-C, VEGF-D, and VEGFR-3 were expressed in a substantial percentage of breast carcinomas. PMID: 28791841
By treating LECs with VEGF-C156S and analyzing subsequent changes in gene expression, we identified several 'immediate early' transcription factors that showed a rapid transient upregulation VEGFR-3 stimulation. these results reveal an important and unanticipated role of HOXD10 in the regulation of VEGFR-3 signaling in lymphatic endothelial cells, and in the control of lymphangiogenesis and permeability. PMID: 27199372
In colon cancer samples, there was a positive correlation between the expression of integrin alpha4 and VEGF-C. Integrin alpha4 and VEGF-C were significantly associated with the clinicopathological parameters (LMVD, Duke's stage, and lymph node metastasis). patients with high integrin alpha4 or VEGF-C expression had significantly shorter overall survival and tumor-free survival time. PMID: 26917449
High VEGFC expression is associated with angiogenesis and lymphangiogenesis. PMID: 27852824
Adiponectin promoted VEGF-C expression and secretion in human chondrosarcoma cells. PMID: 27252405
Study showed that VEGF-C levels are high in hypervolemic and low in euvolemic (and hypovolemic) chronic kidney disease patients; serum VEGF-C levels were significantly correlated with bioimpedance spectroscopy measurements PMID: 28471955
Taken together, we suggest that ELK3 is an upstream regulator of the NF-kappaB signaling pathway, the inhibition of which leads to the suppression of peritumoral lymphatic vessel development, possibly due to a low VEGFC expression. PMID: 28188790
These results indicate that VEGF-C-induced MSC osteogenesis is mediated through VEGFR2 and VEGFR3, and followed the activation of the ERK/RUNX2 signaling pathway. PMID: 28163024
Overexpression of vascular endothelial growth factor C (VEGF-C) in Kazakh esophageal squamous cell carcinoma (ESCC) was significantly associated with gender, depth of tumor invasion, lymph node metastasis and tumor clinical stage. PMID: 27939650
This paper quantifies the lymphatic microvessel density (LMD) in benign and malignant salivary gland tumors and analyzes the relationship between LMD and tumor expression of vascular endothelial growth factors C (VEGF-C) and the proliferative index. PMID: 27229879
KAI1-induced decreases in VEGFC expression are mediated via Src/STAT3 signaling pathways in pancreatic cancer cells. PMID: 27082851
The results of this study suggest that the more aggressive biological behavior of squamous cell carcinoma of the tongue in young patients may be related to a higher expression of VEGF-C. PMID: 27876236
This study suggests that NRP1 expression and LVD are independent factors that are likely to predict the risk of LN metastasis in squamous cell carcinoma (SCC)of the tongue, whereas the expression of VEGFC, VEGFR3, CCR7, and SEMA3E are nonindependent predictive factors PMID: 27666723
High expression of VEGFC is associated with peritoneal dissemination in gastric cancer. PMID: 26621525
TNF-alpha mediates VEGF-C expression, which plays a critical role in the pathogenesis of pterygia. PMID: 27314284
a potential link between the upregulation of Syk and VEGF-C expression and lung adenocarcinoma. PMID: 27461624
The summarizes the structure and function features of pathway-related molecules of VEGFC/D-VEGFR3/NRP2 axis, stages of various tumors and their molecular mechanisms and significances in tuthe expression changes of these molecules in different anatomic organs or histopathologic types or development lymphatic metastasis. PMID: 27527412
Data show that WNT1-inducible signaling pathway protein-1 (WISP)-1/CCN4 expression was correlated with vascular endothelial growth factor-C (VEGF-C) expression in Oral squamous cell carcinoma (OSCC) specimens. PMID: 26824419
VEGF-C overexpression shows an unfavorable prognosis for EC patients. PMID: 27540974
FIGO stage (P < 0.0001), tumor grade (P < 0.0001), lymph node metastasis (P < 0.0001), serum VEGF-C concentration (P = 0.0001), and ascites VEGF-C concentration (P < 0.0001) were significantly correlated with overall survival in ovarian cancer. PMID: 23473018
Our data suggested that IL-6 mediates the singnal pathway of JAK-STAT3-VEGF-C promoting the growth, invasion and lymphangiogenesis in gastric cancer PMID: 26750536
The most extensively accepted signaling pathways promoting lymphangiogenesis in tumors include the secreted lymphangiogenic proteins: VEGF-C and VEGF-D, and their cognate receptor on lymphatic endothelium VEGF receptor-3 (VEGFR-3). PMID: 26706909
the concurrent high expression of VEGF-C and NRP2 is predictive of the unfavorable prognosis in glioblastoma. PMID: 26753562
a significant decrease in miR101 levels, accompanied with an increased expression of vascular endothelial growth factor (VEGF)C in cisplatinresistant SGC7901 gastric cancer cells. PMID: 26573417
MTA1 is up-regulated in CRC; its expression is inversely associated with lymphatic metastases and the expression of VEGFC, VEGFD and VEGFR3 PMID: 26543080
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Involvement in disease
Lymphedema, hereditary, 1D (LMPH1D)
Subcellular Location
Secreted.
Protein Families
PDGF/VEGF growth factor family
Tissue Specificity
Spleen, lymph node, thymus, appendix, bone marrow, heart, placenta, ovary, skeletal muscle, prostate, testis, colon and small intestine and fetal liver, lung and kidney, but not in peripheral blood lymphocyte.