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Gene Review

Vegfc  -  vascular endothelial growth factor C

Mus musculus

Synonyms: AW228853, Flt4 ligand, Flt4-L, VEGF-C, VRP, ...
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Disease relevance of Vegfc


High impact information on Vegfc


Chemical compound and disease context of Vegfc


Biological context of Vegfc


Anatomical context of Vegfc


Associations of Vegfc with chemical compounds

  • The lymphangiogenic vascular endothelial growth factors VEGF-C and -D are ligands for the integrin alpha9beta1 [13].
  • Overexpression of VEGF-C in transfected MCF-7 cells stimulated in vivo tumor growth in xenotransplanted mice without affecting estrogen responsiveness [8].
  • In vivo, Mz-ChA-1 cells were s.c. injected in athymic mice, and the effects of GABA on tumor size, tumor cell proliferation, apoptosis, collagen quantity, and the expression of vascular endothelial growth factor-A (VEGF-A) and VEGF-C (cancer growth regulators) were measured after 82 days [14].
  • In this study we describe the evolution of lymphatic capillaries in regenerating skin and correlate lymphatic migration and organization with the expression of matrix metalloproteinases (MMPs), immune cells, the growth factors VEGF-A and VEGF-C, and the heparan sulfate proteogylcan perlecan, a key component of basement membrane [15].
  • When HB2 cells were stimulated by norepinephrine, the VEGF mRNA level increased without a change in that of VEGF-B, while the VEGF-C mRNA level decreased [16].

Physical interactions of Vegfc

  • As VEGF-C also binds VEGFR-2, which is expressed in lymphatic endothelia, it is not clear which receptors are responsible for the lymphangiogenic effects of VEGF-C [17].

Regulatory relationships of Vegfc


Other interactions of Vegfc


Analytical, diagnostic and therapeutic context of Vegfc

  • By using virus-mediated VEGF-C gene therapy, we were able to generate functional lymphatic vessels in the lymphedema mice [25].
  • In in situ hybridization, mouse VEGF-C mRNA expression was detected in mesenchymal cells of postimplantation mouse embryos, particularly in the regions where the lymphatic vessels undergo sprouting from embryonic veins, such as the perimetanephric, axillary and jugular regions [26].
  • Vascular endothelial growth factor-C promotes vasculogenesis, angiogenesis, and collagen constriction in three-dimensional collagen gels [27].
  • Furthermore, the hyperplasia disappeared when VEGF-C levels diminished, which occurred after 25 days, rendering the lymphatics indistinguishable from those in control groups [28].
  • Ten days after ligation of the external iliac artery, VEGF-C was administered as naked plasmid DNA (pcVEGF-C; 500 microg) from the polymer coating of an angioplasty balloon (n = 8 each) or as recombinant human protein (rhVEGF-C; 500 microg) by direct intra-arterial infusion [29].


  1. Vascular endothelial growth factor C is required for sprouting of the first lymphatic vessels from embryonic veins. Karkkainen, M.J., Haiko, P., Sainio, K., Partanen, J., Taipale, J., Petrova, T.V., Jeltsch, M., Jackson, D.G., Talikka, M., Rauvala, H., Betsholtz, C., Alitalo, K. Nat. Immunol. (2004) [Pubmed]
  2. Suppression of tumor lymphangiogenesis and lymph node metastasis by blocking vascular endothelial growth factor receptor 3 signaling. He, Y., Kozaki, K., Karpanen, T., Koshikawa, K., Yla-Herttuala, S., Takahashi, T., Alitalo, K. J. Natl. Cancer Inst. (2002) [Pubmed]
  3. Vascular endothelial growth factor (VEGF)-C differentially affects tumor vascular function and leukocyte recruitment: role of VEGF-receptor 2 and host VEGF-A. Kadambi, A., Mouta Carreira, C., Yun, C.O., Padera, T.P., Dolmans, D.E., Carmeliet, P., Fukumura, D., Jain, R.K. Cancer Res. (2001) [Pubmed]
  4. Tumor-secreted vascular endothelial growth factor-C is necessary for prostate cancer lymphangiogenesis, but lymphangiogenesis is unnecessary for lymph node metastasis. Wong, S.Y., Haack, H., Crowley, D., Barry, M., Bronson, R.T., Hynes, R.O. Cancer Res. (2005) [Pubmed]
  5. The vascular endothelial growth factor receptor KDR/Flk-1 is a major regulator of malignant ascites formation in the mouse hepatocellular carcinoma model. Yoshiji, H., Kuriyama, S., Hicklin, D.J., Huber, J., Yoshii, J., Ikenaka, Y., Noguchi, R., Nakatani, T., Tsujinoue, H., Fukui, H. Hepatology (2001) [Pubmed]
  6. Cardiovascular failure in mouse embryos deficient in VEGF receptor-3. Dumont, D.J., Jussila, L., Taipale, J., Lymboussaki, A., Mustonen, T., Pajusola, K., Breitman, M., Alitalo, K. Science (1998) [Pubmed]
  7. Hyperplasia of lymphatic vessels in VEGF-C transgenic mice. Jeltsch, M., Kaipainen, A., Joukov, V., Meng, X., Lakso, M., Rauvala, H., Swartz, M., Fukumura, D., Jain, R.K., Alitalo, K. Science (1997) [Pubmed]
  8. VEGF-C induced lymphangiogenesis is associated with lymph node metastasis in orthotopic MCF-7 tumors. Mattila, M.M., Ruohola, J.K., Karpanen, T., Jackson, D.G., Alitalo, K., Härkönen, P.L. Int. J. Cancer (2002) [Pubmed]
  9. Roles of vascular endothelial growth factor receptor 3 signaling in differentiation of mouse embryonic stem cell-derived vascular progenitor cells into endothelial cells. Suzuki, H., Watabe, T., Kato, M., Miyazawa, K., Miyazono, K. Blood (2005) [Pubmed]
  10. Vascular endothelial growth factor-C accelerates diabetic wound healing. Saaristo, A., Tammela, T., Farkkilā, A., Kärkkäinen, M., Suominen, E., Yla-Herttuala, S., Alitalo, K. Am. J. Pathol. (2006) [Pubmed]
  11. VEGF-C is a trophic factor for neural progenitors in the vertebrate embryonic brain. Le Bras, B., Barallobre, M.J., Homman-Ludiye, J., Ny, A., Wyns, S., Tammela, T., Haiko, P., Karkkainen, M.J., Yuan, L., Muriel, M.P., Chatzopoulou, E., Bréant, C., Zalc, B., Carmeliet, P., Alitalo, K., Eichmann, A., Thomas, J.L. Nat. Neurosci. (2006) [Pubmed]
  12. Novel expression of vascular endothelial growth factor receptor (VEGFR)-3 and VEGF-C on corneal dendritic cells. Hamrah, P., Chen, L., Zhang, Q., Dana, M.R. Am. J. Pathol. (2003) [Pubmed]
  13. The lymphangiogenic vascular endothelial growth factors VEGF-C and -D are ligands for the integrin alpha9beta1. Vlahakis, N.E., Young, B.A., Atakilit, A., Sheppard, D. J. Biol. Chem. (2005) [Pubmed]
  14. gamma-Aminobutyric acid inhibits cholangiocarcinoma growth by cyclic AMP-dependent regulation of the protein kinase A/extracellular signal-regulated kinase 1/2 pathway. Fava, G., Marucci, L., Glaser, S., Francis, H., De Morrow, S., Benedetti, A., Alvaro, D., Venter, J., Meininger, C., Patel, T., Taffetani, S., Marzioni, M., Summers, R., Reichenbach, R., Alpini, G. Cancer Res. (2005) [Pubmed]
  15. Characterization of lymphangiogenesis in a model of adult skin regeneration. Rutkowski, J.M., Boardman, K.C., Swartz, M.A. Am. J. Physiol. Heart Circ. Physiol. (2006) [Pubmed]
  16. Isoform-specific regulation of vascular endothelial growth factor (VEGF) family mRNA expression in cultured mouse brown adipocytes. Asano, A., Irie, Y., Saito, M. Mol. Cell. Endocrinol. (2001) [Pubmed]
  17. Signalling via vascular endothelial growth factor receptor-3 is sufficient for lymphangiogenesis in transgenic mice. Veikkola, T., Jussila, L., Makinen, T., Karpanen, T., Jeltsch, M., Petrova, T.V., Kubo, H., Thurston, G., McDonald, D.M., Achen, M.G., Stacker, S.A., Alitalo, K. EMBO J. (2001) [Pubmed]
  18. Enhancement of pleural dissemination and lymph node metastasis of intrathoracic lung cancer cells by vascular endothelial growth factors (VEGFs). Ishii, H., Yazawa, T., Sato, H., Suzuki, T., Ikeda, M., Hayashi, Y., Takanashi, Y., Kitamura, H. Lung Cancer (2004) [Pubmed]
  19. Adenoviral VEGF-C overexpression induces blood vessel enlargement, tortuosity, and leakiness but no sprouting angiogenesis in the skin or mucous membranes. Saaristo, A., Veikkola, T., Enholm, B., Hytönen, M., Arola, J., Pajusola, K., Turunen, P., Jeltsch, M., Karkkainen, M.J., Kerjaschki, D., Bueler, H., Ylä-Herttuala, S., Alitalo, K. FASEB J. (2002) [Pubmed]
  20. Blockade of vascular endothelial growth factor receptor-3 signaling inhibits fibroblast growth factor-2-induced lymphangiogenesis in mouse cornea. Kubo, H., Cao, R., Brakenhielm, E., Mäkinen, T., Cao, Y., Alitalo, K. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  21. VEGF-C, a lymphatic growth factor, is a RANKL target gene in osteoclasts that enhances osteoclastic bone resorption through an autocrine mechanism. Zhang, Q., Guo, R., Lu, Y., Zhao, L., Zhou, Q., Schwarz, E.M., Huang, J., Chen, D., Jin, Z.G., Boyce, B.F., Xing, L. J. Biol. Chem. (2008) [Pubmed]
  22. VEGF-C signaling pathways through VEGFR-2 and VEGFR-3 in vasculoangiogenesis and hematopoiesis. Hamada, K., Oike, Y., Takakura, N., Ito, Y., Jussila, L., Dumont, D.J., Alitalo, K., Suda, T. Blood (2000) [Pubmed]
  23. p42/p44 MAP kinase module plays a key role in the transcriptional regulation of the vascular endothelial growth factor gene in fibroblasts. Milanini, J., Viñals, F., Pouysségur, J., Pagès, G. J. Biol. Chem. (1998) [Pubmed]
  24. Expression of the VEGF gene family during retinal vaso-obliteration and hypoxia. Simpson, D.A., Murphy, G.M., Bhaduri, T., Gardiner, T.A., Archer, D.B., Stitt, A.W. Biochem. Biophys. Res. Commun. (1999) [Pubmed]
  25. A model for gene therapy of human hereditary lymphedema. Karkkainen, M.J., Saaristo, A., Jussila, L., Karila, K.A., Lawrence, E.C., Pajusola, K., Bueler, H., Eichmann, A., Kauppinen, R., Kettunen, M.I., Yla-Herttuala, S., Finegold, D.N., Ferrell, R.E., Alitalo, K. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  26. VEGF-C receptor binding and pattern of expression with VEGFR-3 suggests a role in lymphatic vascular development. Kukk, E., Lymboussaki, A., Taira, S., Kaipainen, A., Jeltsch, M., Joukov, V., Alitalo, K. Development (1996) [Pubmed]
  27. Vascular endothelial growth factor-C promotes vasculogenesis, angiogenesis, and collagen constriction in three-dimensional collagen gels. Bauer, S.M., Bauer, R.J., Liu, Z.J., Chen, H., Goldstein, L., Velazquez, O.C. J. Vasc. Surg. (2005) [Pubmed]
  28. Overexpression of VEGF-C causes transient lymphatic hyperplasia but not increased lymphangiogenesis in regenerating skin. Goldman, J., Le, T.X., Skobe, M., Swartz, M.A. Circ. Res. (2005) [Pubmed]
  29. Vascular endothelial growth factor-C (VEGF-C/VEGF-2) promotes angiogenesis in the setting of tissue ischemia. Witzenbichler, B., Asahara, T., Murohara, T., Silver, M., Spyridopoulos, I., Magner, M., Principe, N., Kearney, M., Hu, J.S., Isner, J.M. Am. J. Pathol. (1998) [Pubmed]
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