vascular endothelial growth factor c


Summary: A vascular endothelial growth factor that specifically binds to VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR-2 and VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR-3. In addition to being an angiogenic factor it can act on LYMPHATIC VESSELS to stimulate LYMPHANGIOGENESIS. It is similar in structure to VASCULAR ENDOTHELIAL GROWTH FACTOR D in that they both contain N- and C-terminal extensions that were not found in other VEGF family members.

Top Publications

  1. Böhmer R, Neuhaus B, Bühren S, Zhang D, Stehling M, Böck B, et al. Regulation of developmental lymphangiogenesis by Syk(+) leukocytes. Dev Cell. 2010;18:437-49 pubmed publisher
    ..This mechanism does not involve circulating endothelial progenitor cells and demonstrates the potential of hematopoietic cells to control developmental lymphangiogenesis. ..
  2. Tvorogov D, Anisimov A, Zheng W, Leppänen V, Tammela T, Laurinavicius S, et al. Effective suppression of vascular network formation by combination of antibodies blocking VEGFR ligand binding and receptor dimerization. Cancer Cell. 2010;18:630-40 pubmed publisher
    ..These results suggest that receptor dimerization inhibitors could be used to enhance antiangiogenic activity of antibodies blocking ligand binding in tumor therapy. ..
  3. Albuquerque R, Hayashi T, Cho W, Kleinman M, Dridi S, Takeda A, et al. Alternatively spliced vascular endothelial growth factor receptor-2 is an essential endogenous inhibitor of lymphatic vessel growth. Nat Med. 2009;15:1023-30 pubmed publisher
  4. Tammela T, Saaristo A, Holopainen T, Lyytikkä J, Kotronen A, Pitkonen M, et al. Therapeutic differentiation and maturation of lymphatic vessels after lymph node dissection and transplantation. Nat Med. 2007;13:1458-66 pubmed
    ..These results show that growth factor-induced maturation of lymphatic vessels is possible in adult mice and provide a basis for future therapy of lymphedema. ..
  5. Mishima K, Watabe T, Saito A, Yoshimatsu Y, Imaizumi N, Masui S, et al. Prox1 induces lymphatic endothelial differentiation via integrin alpha9 and other signaling cascades. Mol Biol Cell. 2007;18:1421-9 pubmed
  6. Min Y, Ghose S, Boelte K, Li J, Yang L, Lin P. C/EBP-? regulates VEGF-C autocrine signaling in lymphangiogenesis and metastasis of lung cancer through HIF-1?. Oncogene. 2011;30:4901-9 pubmed publisher
    ..Blocking HIF-1? activity totally blocked CEBP-?-induced VEGF-C and VEGFR3 expression in LECs. Together, these findings uncover a new function of CEBP-? in lymphangiogenesis through regulation of VEGFR3 signaling in LECs. ..
  7. Ye J, Wu X, Wu D, Wu P, Ni C, Zhang Z, et al. miRNA-27b targets vascular endothelial growth factor C to inhibit tumor progression and angiogenesis in colorectal cancer. PLoS ONE. 2013;8:e60687 pubmed publisher
    ..We identified vascular endothelial growth factor C (VEGFC) as a novel target gene of miR-27b and determined that miR-27b functioned as an inhibitor of ..
  8. Kumar B, Chile S, Ray K, Reddy G, Addepalli M, Kumar A, et al. VEGF-C differentially regulates VEGF-A expression in ocular and cancer cells; promotes angiogenesis via RhoA mediated pathway. Angiogenesis. 2011;14:371-80 pubmed publisher
    ..Further, knockdown studies of RhoA even with supplementation of VEGF-C or A has resulted in decreased endothelial cell proliferation and stress fiber formation, indicating that VEGF-C does promote angiogenesis via RhoA mediated pathway. ..
  9. Piltonen M, Planken A, Leskelä O, Myöhänen T, Hänninen A, Auvinen P, et al. Vascular endothelial growth factor C acts as a neurotrophic factor for dopamine neurons in vitro and in vivo. Neuroscience. 2011;192:550-63 pubmed publisher
    ..Our results provide evidence of VEGF-C as a neurotrophic factor that influences the dopaminergic system through multiple mechanisms. ..

More Information


  1. Bos F, Caunt M, Peterson Maduro J, Planas Paz L, Kowalski J, Karpanen T, et al. CCBE1 is essential for mammalian lymphatic vascular development and enhances the lymphangiogenic effect of vascular endothelial growth factor-C in vivo. Circ Res. 2011;109:486-91 pubmed publisher
    ..Insight into the molecular role of CCBE1 is completely lacking, and mouse models for the disease do not exist...
  2. Khromova N, Kopnin P, Rybko V, Kopnin B. Downregulation of VEGF-C expression in lung and colon cancer cells decelerates tumor growth and inhibits metastasis via multiple mechanisms. Oncogene. 2012;31:1389-97 pubmed publisher
    ..These results are consistent with the idea of high potentiality of VEGF-C as a cancer drug target. ..
  3. Chaudary N, Milosevic M, Hill R. Suppression of vascular endothelial growth factor receptor 3 (VEGFR3) and vascular endothelial growth factor C (VEGFC) inhibits hypoxia-induced lymph node metastases in cervix cancer. Gynecol Oncol. 2011;123:393-400 pubmed publisher
    ..These results suggest that the effects of vegfc/VEGFR3 on the progression of tumor cells to form lymph node metastases occur primarily under an hypoxic tumor microenvironment. ..
  4. Nitta A, Shirasuna K, Haneda S, Matsui M, Shimizu T, Matsuyama S, et al. Possible involvement of IFNT in lymphangiogenesis in the corpus luteum during the maternal recognition period in the cow. Reproduction. 2011;142:879-92 pubmed publisher
    ..Moreover, both IFNT and VEGFC induced LyECs to form capillary-like tubes in vitro. In conclusion, it is suggested that new lymphangiogenesis in the bovine CL begins during the MRP and that IFNT may mediate this novel phenomenon...
  5. Inamine M, Nagai Y, Mitsuhashi A, Nagase S, Yaegashi N, Yoshikawa H, et al. Cigarette smoke stimulates VEGF-C expression in cervical intraepithelial neoplasia (CIN) 1 and 2 lesions. Int J Clin Oncol. 2012;17:498-504 pubmed publisher
    ..No significant difference was observed among the HPV risk groups in both average Ki-67 and VEGF-C expression. These findings suggest that VEGF-C may play an important role in cigarette smoking-associated cervical carcinogenesis. ..
  6. Feng L, Zheng X, Zhou L, Fu B, Yu Y, Lu S, et al. Correlation between expression of S100A4 and VEGF-C, and lymph node metastasis and prognosis in gastric carcinoma. J Int Med Res. 2011;39:1333-43 pubmed
    This semiquantitative immunohistochemical study investigated the clinical significance of S100A4 and vascular endothelial growth factor C (VEGF-C) protein expression in gastric carcinoma...
  7. Zhang H, Yin Y, Zhang L, Zheng X, Gao D, Chen K, et al. The effects of vascular endothelial growth factor C knockdown in esophageal squamous cell carcinoma. J Cancer Res Clin Oncol. 2012;138:133-9 pubmed publisher
    We investigated the role of vascular endothelial growth factor C (VEGF-C) in esophageal squamous cell carcinoma (ESCC) by knocking down VEGF-C expression in the ESCC cell line EC9706...
  8. Wada H, Ura S, Kitaoka S, Satoh Asahara N, Horie T, Ono K, et al. Distinct characteristics of circulating vascular endothelial growth factor-a and C levels in human subjects. PLoS ONE. 2011;6:e29351 pubmed publisher
    ..In conclusion, these findings demonstrate that VEGF-C, rather than VEGF-A, is closely related to dyslipidemia and atherosclerosis. ..
  9. Lund A, Durães F, Hirosue S, Raghavan V, Nembrini C, Thomas S, et al. VEGF-C promotes immune tolerance in B16 melanomas and cross-presentation of tumor antigen by lymph node lymphatics. Cell Rep. 2012;1:191-9 pubmed publisher
    ..Our findings introduce a tumor-promoting role for lymphatics in the tumor and dLN and suggest that lymphatic endothelium in the local microenvironment may be a target for immunomodulation...
  10. Zhao Y, Ni X, Li Y, Dai M, Yuan Z, Zhu Y, et al. Peritumoral lymphangiogenesis induced by vascular endothelial growth factor C and D promotes lymph node metastasis in breast cancer patients. World J Surg Oncol. 2012;10:165 pubmed publisher
  11. Zhao D, Wang S, Feng Y, Hua C, Zhao J, Tang X. Intratumoral c-Met expression is associated with vascular endothelial growth factor C expression, lymphangiogenesis, and lymph node metastasis in oral squamous cell carcinoma: implications for use as a prognostic marker. Hum Pathol. 2011;42:1514-23 pubmed publisher
    ..vessel density, lymphatic invasion, the expression of hepatocyte growth factor, c-Met, and vascular endothelial growth factor C proteins were evaluated by immunohistochemistry in 76 cases of oral squamous cell carcinoma...
  12. Huggenberger R, Siddiqui S, Brander D, Ullmann S, Zimmermann K, Antsiferova M, et al. An important role of lymphatic vessel activation in limiting acute inflammation. Blood. 2011;117:4667-78 pubmed publisher
    ..These results provide evidence that specific lymphatic vessel activation limits acute skin inflammation via promotion of lymph flow from the skin and reduction of edema formation. ..
  13. Gou H, Chen X, Zhu J, Jiang M, Yang Y, Cao D, et al. Expressions of COX-2 and VEGF-C in gastric cancer: correlations with lymphangiogenesis and prognostic implications. J Exp Clin Cancer Res. 2011;30:14 pubmed publisher
    ..This study aims to test the expression of COX-2 and VEGF-C in human gastric cancer, and to analyze the correlation with lymphatic vessel density (LVD), clinicopathologic features and survival prognosis...
  14. Leppänen V, Jeltsch M, Anisimov A, Tvorogov D, Aho K, Kalkkinen N, et al. Structural determinants of vascular endothelial growth factor-D receptor binding and specificity. Blood. 2011;117:1507-15 pubmed publisher
    ..Thus, we define here a VEGFR-2-specific form of VEGF-D that is angiogenic but not lymphangiogenic. These results provide important new insights into VEGF-D structure and function. ..
  15. Chen X, Xie Q, Cheng X, Diao X, Cheng Y, Liu J, et al. Role of interleukin-17 in lymphangiogenesis in non-small-cell lung cancer: Enhanced production of vascular endothelial growth factor C in non-small-cell lung carcinoma cells. Cancer Sci. 2010;101:2384-90 pubmed publisher
    ..We conclude that IL-17 is involved in lymphangiogenesis in NSCLC by enhancing production of VEGF-C, and IL-17 may be an important target for the treatment of NSCLC. ..
  16. Chen Y, Jiang L, She F, Tang N, Wang X, Li X, et al. Vascular endothelial growth factor-C promotes the growth and invasion of gallbladder cancer via an autocrine mechanism. Mol Cell Biochem. 2010;345:77-89 pubmed publisher
    ..In conclusion, GBC cells express both VEGF-C and its receptors. VEGF-C may have a role in the progressive growth and invasion of human GBC through an autocrine mechanism...
  17. Zheng S, Huang R, Zhang Y. [Role of matrix metalloproteinase (MMP)-2 and -9 and vascular endothelial growth factor C in lymph node metastasis of breast cancer]. Zhonghua Bing Li Xue Za Zhi. 2010;39:240-4 pubmed
    ..The expression of MMP-2, MMP-9 and VEGF-C in MCF-7 cells after gene transfection decreased significantly (P < 0.05). MMP-2 and MMP-9 in conjunction with VEGF-C, promote lymphangiogenesis and lymph node metastasis of breast cancer. ..
  18. Bhattacharjee R, Timoshenko A, Cai J, Lala P. Relationship between cyclooxygenase-2 and human epidermal growth factor receptor 2 in vascular endothelial growth factor C up-regulation and lymphangiogenesis in human breast cancer. Cancer Sci. 2010;101:2026-32 pubmed publisher
  19. Tanaka T, Ishiguro H, Kuwabara Y, Kimura M, Mitsui A, Katada T, et al. Vascular endothelial growth factor C (VEGF-C) in esophageal cancer correlates with lymph node metastasis and poor patient prognosis. J Exp Clin Cancer Res. 2010;29:83 pubmed publisher
    ..In addition, the indication of non-surgical therapy is gaining more attention. Vascular endothelial growth factor C (VEGF-C) is potentially lymphangiogenic and selectively induces hyperplasia of the lymphatic ..
  20. Wang X, Fang J, Tang R, Chen X. Different significance between intratumoral and peritumoral lymphatic vessel density in gastric cancer: a retrospective study of 123 cases. BMC Cancer. 2010;10:299 pubmed publisher
    ..Increased P-LVD, but not I-LVD, was significantly associated with VEGF-C/-D/VEGFR-3 system, and could be an independent risk factor for lymph node metastasis and a prognostic factor in gastric cancer. ..
  21. He M, Cheng Y, Li W, Liu Q, Liu J, Huang J, et al. Vascular endothelial growth factor C promotes cervical cancer metastasis via up-regulation and activation of RhoA/ROCK-2/moesin cascade. BMC Cancer. 2010;10:170 pubmed publisher
    The elevated expression of vascular endothelial growth factor C (VEGF-C) is correlated with clinical cervical cancer metastasis and patient survival, which is interpreted by VEGF-C functions to stimulate angiogenesis and lymphatic genesis...
  22. Feng Y, Wang W, Hu J, Ma J, Zhang Y, Zhang J. Expression of VEGF-C and VEGF-D as significant markers for assessment of lymphangiogenesis and lymph node metastasis in non-small cell lung cancer. Anat Rec (Hoboken). 2010;293:802-12 pubmed publisher
  23. Benest A, Harper S, Herttuala S, Alitalo K, Bates D. VEGF-C induced angiogenesis preferentially occurs at a distance from lymphangiogenesis. Cardiovasc Res. 2008;78:315-23 pubmed
    ..These results both demonstrate a dependence of VEGF-C-mediated angiogenesis on lymphatic vascular networks and indicate that the mechanism of VEGF-C-mediated lymphangiogenesis is different from that of classical angiogenic mechanisms. ..