请输入您要查询的百科知识：

　

词条 Vascular endothelial growth factor C
释义

  1. Functions

  2. Biosynthesis

  3. Relationship to VEGF-D

  4. Disease relevance

  5. Evolution

  6. References

  7. Further reading

{{Infobox_gene}}Vascular endothelial growth factor C (VEGF-C) is a protein that is a member of the platelet-derived growth factor / vascular endothelial growth factor (PDGF/VEGF) family. It is encoded in humans by the VEGFC gene, which is located on chromosome 4q34.[1]

Functions

The main function of VEGF-C is in lymphangiogenesis, where it acts on lymphatic endothelial cells (LECs) primarily via its receptor VEGFR-3 promoting survival, growth and migration. It was discovered in 1996 as a ligand for the orphan receptor VEGFR-3.[2] Soon thereafter, it was shown to be a specific growth factor for lymphatic vessels in a variety of models.[3][4] However, in addition to its effect on lymphatic vessels, it can also promote the growth of blood vessels and regulate their permeability. The effect on blood vessels can be mediated via its primary receptor VEGFR-3[5] or its secondary receptor VEGFR-2. Apart from vascular targets, VEGF-C is also important for neural development[6] and blood pressure regulation.[7] It has been suggested that VEGFC is a morphogen but not a chemotactic factor for lymphatic endothelial cell precursors.[8]

It has been suggested that VEGFC can form Turing patterns to regulate lymphangiogenesis in the zebrafish embryo by interacting with collagen I and MMP2 .[9]

Biosynthesis

VEGF-C is a dimeric, secreted protein, which undergoes a complex proteolytic maturation resulting in multiple processed forms. After translation, VEGF-C consists of three domains: the central VEGF homology domain (VHD), the N-terminal domain (propeptide) and a C-terminal domain (propeptide).[10] It is referred to as "uncleaved VEGF-C" and has a size of approximately 58 kDa. The first cleavage (which happens already before secretion) occurs between the VHD and the C-terminal domain and is mediated by proprotein convertases.[11] However, the resulting protein is still held together by disulfide bonds and remains inactive (although it can bind already VEGFR-3).[12] This form is referred to as "intermediate form" or pro-VEGF-C and it consists of two polypeptide chains of 29 and 31 kDa. In order to activate VEGF-C, a second cleavage has to occur between the N-terminal propeptide and the VHD. This cleavage can be performed either by ADAMTS3[12] or plasmin.[13] With progressing maturation, the affinity of VEGF-C for both VEGFR-2 and VEGFR-3 increases and only the fully processed, mature forms of VEGF-C have a significant affinity for VEGFR-2.[10]

Relationship to VEGF-D

The closest structural and functional relative of VEGF-C is VEGF-D.[14] However, at least in mice, VEGF-C is absolutely essential for the development of the lymphatic system,[15] whereas VEGF-D appears to be not necessary at all.[16] Whether this holds true for humans is unknown, because there are major differences between human and mouse VEGF-D.[17]

Disease relevance

In a minority of lymphedema patients, the condition is caused by mutations in the VEGFC gene[18] and VEGF-C is a potential treatment for lymphedema,[19][20] even though the underlying molecular cause appears more often in the VEGF-Receptor-3 instead of VEGF-C itself.[21] Because in Milroy's disease (Hereditary lymphedema type I), only one allele is mutated, not all VEGFR-3 molecules are non-functional and it is thought, that high amounts of VEGF-C can compensate for the mutated, nonfunctional receptors by increasing the signaling levels of the remaining functional receptors.[22] Therefore VEGF-C is developed as a lymphedema drug under the name of Lymfactin.[23] Also indirectly VEGF-C can be responsible for hereditary lymphedema: The rare Hennekam syndrome can result from the inability of the mutated CCBE1 to assist the ADAMTS3 protease in activating VEGF-C.[12] While a lack of VEGF-C results in lymphedema, too much VEGF-C is implicated in tumor angiogenesis and metastasis. VEGF-C can act directly on blood vessels to promote tumor angiogenesis[5][24] and it can promote lymphangiogenesis, which might result in increased metastasis.[25]

Evolution

The PDGF family is so closely related to the VEGF family that the two are sometimes grouped together as the PDGF/VEGF family. In invertebrates, molecules from this families are not easily distinguished from each other and are collectively referred to as PVFs (PDGF/VEGF-like growth factors.[26] The comparison of human VEGFs with these PVFs allows conclusions on the structure of the ancestral molecules, which appear more closely related to today's lymphangiogenic VEGF-C than to the other members of the VEGF family and despite their large evolutionary distance are still able to interact with human VEGF receptors. The PVFs in Drosophila melanogaster have functions for the migration of hemocytes[27] and the PVFs in the jellyfish Podocoryne carnea for the development of the tentacles and the gastrovascular apparatus.[28] However, the function of the PVF-1 of the nematode Caenorhabditis elegans is unknown[26]

References

1. ^{{cite journal | vauthors = Paavonen K, Horelli-Kuitunen N, Chilov D, Kukk E, Pennanen S, Kallioniemi OP, Pajusola K, Olofsson B, Eriksson U, Joukov V, Palotie A, Alitalo K | title = Novel human vascular endothelial growth factor genes VEGF-B and VEGF-C localize to chromosomes 11q13 and 4q34, respectively | journal = Circulation | volume = 93 | issue = 6 | pages = 1079–1082 | date = Mar 1996 | pmid = 8653826 | doi = 10.1161/01.CIR.93.6.1079 }}
2. ^{{cite journal | vauthors = Joukov V, Pajusola K, Kaipainen A, Chilov D, Lahtinen I, Kukk E, Saksela O, Kalkkinen N, Alitalo K | title = A novel vascular endothelial growth factor, VEGF-C, is a ligand for the Flt4 (VEGFR-3) and KDR (VEGFR-2) receptor tyrosine kinases | journal = The EMBO Journal | volume = 15 | issue = 2 | pages = 290–298 | date = Jan 1996 | pmid = 8617204 | pmc = 449944 | doi = 10.1002/j.1460-2075.1996.tb00359.x }}
3. ^{{cite journal | vauthors = Oh SJ, Jeltsch MM, Birkenhäger R, McCarthy JE, Weich HA, Christ B, Alitalo K, Wilting J | title = VEGF and VEGF-C: specific induction of angiogenesis and lymphangiogenesis in the differentiated avian chorioallantoic membrane | journal = Developmental Biology | volume = 188 | issue = 1 | pages = 96–109 | date = Aug 1997 | pmid = 9245515 | doi = 10.1006/dbio.1997.8639 }}
4. ^{{cite journal | vauthors = Jeltsch M, Kaipainen A, Joukov V, Meng X, Lakso M, Rauvala H, Swartz M, Fukumura D, Jain RK, Alitalo K | title = Hyperplasia of lymphatic vessels in VEGF-C transgenic mice | journal = Science | volume = 276 | issue = 5317 | pages = 1423–1425 | date = May 1997 | pmid = 9162011 | doi = 10.1126/science.276.5317.1423 }}
5. ^1 {{cite journal | vauthors = Tammela T, Zarkada G, Wallgard E, Murtomäki A, Suchting S, Wirzenius M, Waltari M, Hellström M, Schomber T, Peltonen R, Freitas C, Duarte A, Isoniemi H, Laakkonen P, Christofori G, Ylä-Herttuala S, Shibuya M, Pytowski B, Eichmann A, Betsholtz C, Alitalo K | title = Blocking VEGFR-3 suppresses angiogenic sprouting and vascular network formation | journal = Nature | volume = 454 | issue = 7204 | pages = 656–660 | date = Jul 2008 | pmid = 18594512 | doi = 10.1038/nature07083 }}
6. ^{{cite journal | vauthors = Le Bras B, Barallobre MJ, Homman-Ludiye J, Ny A, Wyns S, Tammela T, Haiko P, Karkkainen MJ, Yuan L, Muriel MP, Chatzopoulou E, Bréant C, Zalc B, Carmeliet P, Alitalo K, Eichmann A, Thomas JL | title = VEGF-C is a trophic factor for neural progenitors in the vertebrate embryonic brain | journal = Nature Neuroscience | volume = 9 | issue = 3 | pages = 340–348 | date = Mar 2006 | pmid = 16462734 | doi = 10.1038/nn1646 }}
7. ^{{cite journal | vauthors = Machnik A, Neuhofer W, Jantsch J, Dahlmann A, Tammela T, Machura K, Park JK, Beck FX, Müller DN, Derer W, Goss J, Ziomber A, Dietsch P, Wagner H, van Rooijen N, Kurtz A, Hilgers KF, Alitalo K, Eckardt KU, Luft FC, Kerjaschki D, Titze J | title = Macrophages regulate salt-dependent volume and blood pressure by a vascular endothelial growth factor-C-dependent buffering mechanism | journal = Nature Medicine | volume = 15 | issue = 5 | pages = 545–552 | date = May 2009 | pmid = 19412173 | doi = 10.1038/nm.1960 }}
8. ^{{Cite journal|last=Wertheim|first=Kenneth Y.|last2=Roose|first2=Tiina|date=April 2017|title=A Mathematical Model of Lymphangiogenesis in a Zebrafish Embryo|journal=Bulletin of Mathematical Biology|volume=79|issue=4|pages=693–737|doi=10.1007/s11538-017-0248-7|issn=1522-9602|pmc=5501200|pmid=28233173}}
9. ^{{Cite journal|last=Roose|first=Tiina|last2=Wertheim|first2=Kenneth Y.|date=2019-01-03|title=Can VEGFC Form Turing Patterns in the Zebrafish Embryo?|journal=Bulletin of Mathematical Biology|language=en|pages=1–37|doi=10.1007/s11538-018-00560-2|pmid=30607882|issn=1522-9602}}
10. ^1 {{cite journal | vauthors = Joukov V, Sorsa T, Kumar V, Jeltsch M, Claesson-Welsh L, Cao Y, Saksela O, Kalkkinen N, Alitalo K | title = Proteolytic processing regulates receptor specificity and activity of VEGF-C | journal = The EMBO Journal | volume = 16 | issue = 13 | pages = 3898–3911 | date = Jul 1997 | pmid = 9233800 | doi = 10.1093/emboj/16.13.3898 | pmc=1170014}}
11. ^{{cite journal | vauthors = Siegfried G, Basak A, Cromlish JA, Benjannet S, Marcinkiewicz J, Chrétien M, Seidah NG, Khatib AM | title = The secretory proprotein convertases furin, PC5, and PC7 activate VEGF-C to induce tumorigenesis | journal = The Journal of Clinical Investigation | volume = 111 | issue = 11 | pages = 1723–1732 | date = Jun 2003 | pmid = 12782675 | doi = 10.1172/JCI17220 | pmc=156106}}
12. ^1 2 {{cite journal | vauthors = Jeltsch M, Jha SK, Tvorogov D, Anisimov A, Leppänen VM, Holopainen T, Kivelä R, Ortega S, Kärpanen T, Alitalo K | title = CCBE1 enhances lymphangiogenesis via A disintegrin and metalloprotease with thrombospondin motifs-3-mediated vascular endothelial growth factor-C activation | journal = Circulation | volume = 129 | issue = 19 | pages = 1962–1971 | date = May 2014 | pmid = 24552833 | doi = 10.1161/CIRCULATIONAHA.113.002779 }}
13. ^{{cite journal | vauthors = McColl BK, Baldwin ME, Roufail S, Freeman C, Moritz RL, Simpson RJ, Alitalo K, Stacker SA, Achen MG | title = Plasmin activates the lymphangiogenic growth factors VEGF-C and VEGF-D | journal = The Journal of Experimental Medicine | volume = 198 | issue = 6 | pages = 863–868 | date = Sep 2003 | pmid = 12963694 | pmc = 2194198 | doi = 10.1084/jem.20030361 }}
14. ^{{cite journal | vauthors = Achen MG, Jeltsch M, Kukk E, Mäkinen T, Vitali A, Wilks AF, Alitalo K, Stacker SA | title = Vascular endothelial growth factor D (VEGF-D) is a ligand for the tyrosine kinases VEGF receptor 2 (Flk1) and VEGF receptor 3 (Flt4) | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 95 | issue = 2 | pages = 548–553 | date = Jan 1998 | pmid = 9435229 | doi=10.1073/pnas.95.2.548 | pmc=18457}}
15. ^{{cite journal | vauthors = Karkkainen MJ, Haiko P, Sainio K, Partanen J, Taipale J, Petrova TV, Jeltsch M, Jackson DG, Talikka M, Rauvala H, Betsholtz C, Alitalo K | title = Vascular endothelial growth factor C is required for sprouting of the first lymphatic vessels from embryonic veins | journal = Nature Immunology | volume = 5 | issue = 1 | pages = 74–80 | date = Jan 2004 | pmid = 14634646 | doi = 10.1038/ni1013 }}
16. ^{{cite journal | vauthors = Baldwin ME, Halford MM, Roufail S, Williams RA, Hibbs ML, Grail D, Kubo H, Stacker SA, Achen MG | title = Vascular endothelial growth factor D is dispensable for development of the lymphatic system | journal = Molecular and Cellular Biology | volume = 25 | issue = 6 | pages = 2441–2449 | date = Mar 2005 | pmid = 15743836 | doi = 10.1128/MCB.25.6.2441-2449.2005 | pmc=1061605}}
17. ^{{cite journal | vauthors = Baldwin ME, Catimel B, Nice EC, Roufail S, Hall NE, Stenvers KL, Karkkainen MJ, Alitalo K, Stacker SA, Achen MG | title = The specificity of receptor binding by vascular endothelial growth factor-d is different in mouse and man | journal = The Journal of Biological Chemistry | volume = 276 | issue = 22 | pages = 19166–19171 | date = Jun 2001 | pmid = 11279005 | doi = 10.1074/jbc.M100097200 }}
18. ^{{cite journal | vauthors = Balboa-Beltran E, Fernández-Seara MJ, Pérez-Muñuzuri A, Lago R, García-Magán C, Couce ML, Sobrino B, Amigo J, Carracedo A, Barros F | title = A novel stop mutation in the vascular endothelial growth factor-C gene (VEGFC) results in Milroy-like disease | journal = Journal of Medical Genetics | volume = 51 | issue = 7 | pages = 475–8 | date = Jul 2014 | pmid = 24744435 | doi = 10.1136/jmedgenet-2013-102020 }}
19. ^{{cite journal | vauthors = Enholm B, Karpanen T, Jeltsch M, Kubo H, Stenback F, Prevo R, Jackson DG, Yla-Herttuala S, Alitalo K | title = Adenoviral expression of vascular endothelial growth factor-C induces lymphangiogenesis in the skin | journal = Circulation Research | volume = 88 | issue = 6 | pages = 623–629 | date = Mar 2001 | pmid = 11282897 | doi = 10.1161/01.RES.88.6.623 }}
20. ^{{cite journal | vauthors = Honkonen KM, Visuri MT, Tervala TV, Halonen PJ, Koivisto M, Lähteenvuo MT, Alitalo KK, Ylä-Herttuala S, Saaristo AM | title = Lymph node transfer and perinodal lymphatic growth factor treatment for lymphedema | journal = Annals of Surgery | volume = 257 | issue = 5 | pages = 961–967 | date = May 2013 | pmid = 23013803 | doi = 10.1097/SLA.0b013e31826ed043 }}
21. ^{{cite journal | vauthors = Brouillard P, Boon L, Vikkula M | title = Genetics of lymphatic anomalies | journal = The Journal of Clinical Investigation | volume = 124 | issue = 3 | pages = 898–904 | date = Mar 2014 | pmid = 24590274 | doi = 10.1172/JCI71614 | pmc=3938256}}
22. ^{{cite journal | vauthors = Karkkainen MJ, Saaristo A, Jussila L, Karila KA, Lawrence EC, Pajusola K, Bueler H, Eichmann A, Kauppinen R, Kettunen MI, Yla-Herttuala S, Finegold DN, Ferrell RE, Alitalo K | title = A model for gene therapy of human hereditary lymphedema | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 98 | issue = 22 | pages = 12677–12682 | date = Oct 2001 | pmid = 11592985 | doi = 10.1073/pnas.221449198 | pmc=60113}}
23. ^{{cite web| last = Herantis Pharma| title = Lymfactin® for lymphedema| date = 2014-07-21}}
24. ^{{cite journal | vauthors = Tvorogov D, Anisimov A, Zheng W, Leppänen VM, Tammela T, Laurinavicius S, Holnthoner W, Heloterä H, Holopainen T, Jeltsch M, Kalkkinen N, Lankinen H, Ojala PM, Alitalo K | title = Effective suppression of vascular network formation by combination of antibodies blocking VEGFR ligand binding and receptor dimerization | journal = Cancer Cell | volume = 18 | issue = 6 | pages = 630–640 | date = Dec 2010 | pmid = 21130043 | doi = 10.1016/j.ccr.2010.11.001 }}
25. ^{{cite journal | vauthors = Mandriota SJ, Jussila L, Jeltsch M, Compagni A, Baetens D, Prevo R, Banerji S, Huarte J, Montesano R, Jackson DG, Orci L, Alitalo K, Christofori G, Pepper MS | title = Vascular endothelial growth factor-C-mediated lymphangiogenesis promotes tumour metastasis | journal = The EMBO Journal | volume = 20 | issue = 4 | pages = 672–682 | date = Feb 2001 | pmid = 11179212 | doi = 10.1093/emboj/20.4.672 | pmc=145430}}
26. ^1 {{cite journal | vauthors = Tarsitano M, De Falco S, Colonna V, McGhee JD, Persico MG | title = The C. elegans pvf-1 gene encodes a PDGF/VEGF-like factor able to bind mammalian VEGF receptors and to induce angiogenesis | journal = FASEB Journal | volume = 20 | issue = 2 | pages = 227–233 | date = Feb 2006 | pmid = 16449794 | doi = 10.1096/fj.05-4147com }}
27. ^{{cite journal | vauthors = Heino TI, Kärpänen T, Wahlström G, Pulkkinen M, Eriksson U, Alitalo K, Roos C | title = The Drosophila VEGF receptor homolog is expressed in hemocytes | journal = Mechanisms of Development | volume = 109 | issue = 1 | pages = 69–77 | date = Nov 2001 | pmid = 11677054 | doi = 10.1016/S0925-4773(01)00510-X }}
28. ^{{cite journal | vauthors = Seipel K, Eberhardt M, Müller P, Pescia E, Yanze N, Schmid V | title = Homologs of vascular endothelial growth factor and receptor, VEGF and VEGFR, in the jellyfish Podocoryne carnea | journal = Developmental Dynamics | volume = 231 | issue = 2 | pages = 303–312 | date = Oct 2004 | pmid = 15366007 | doi = 10.1002/dvdy.20139 }}

Further reading

{{refbegin|33em}}
  • {{cite journal | vauthors = Rauniyar K, Jha SK, Jeltsch M | title = Biology of Vascular Endothelial Growth Factor C in the Morphogenesis of Lymphatic Vessels | journal = Frontiers in Bioengineering and Biotechnology | volume = 6 | pages = 7 | date = Feb 2018 | doi = 10.3389/fbioe.2018.00007 | pmid = 29484295 | pmc = 5816233 }}
  • {{cite journal | vauthors = Krebs R, Jeltsch M | title = The lymphangiogenic growth factors VEGF-C and VEGF-D. Part 1: Basic principles and embryonic development | journal = Lymphologie in Forschung und Praxis | volume = 17 | issue = 1 | pages = 30–37 | date = June 2013 | url = https://jeltsch.org/sites/jeltsch.org/files/krebsjeltschlymphforsch200317130-37-150406160631-conversion-gate01.pdf }}
  • {{cite journal | vauthors = Krebs R, Jeltsch M | title = Die lymphangiogenic growth factors VEGF-C and VEGF-D. Part 2: The role of VEGF-C and VEGF-D in diseases of the lymphatic system | journal = Lymphologie in Forschung und Praxis | volume = 17 | issue = 2 | pages = 96–104 | date = Dec 2013 | url = https://jeltsch.org/sites/jeltsch.org/files/Krebs%26Jeltsch_Lymphforsch_2013_17%282%2996-104.pdf }}
  • {{cite journal | vauthors = Orpana A, Salven P | title = Angiogenic and lymphangiogenic molecules in hematological malignancies | journal = Leukemia & Lymphoma | volume = 43 | issue = 2 | pages = 219–24 | date = Feb 2002 | pmid = 11999550 | doi = 10.1080/10428190290005964 }}
  • {{cite journal | vauthors = Orpana A, Salven P | title = Angiogenic and lymphangiogenic molecules in hematological malignancies | journal = Leukemia & Lymphoma | volume = 43 | issue = 2 | pages = 219–24 | date = Feb 2002 | pmid = 11999550 | doi = 10.1080/10428190290005964 }}
  • {{cite journal | vauthors = Joukov V, Pajusola K, Kaipainen A, Chilov D, Lahtinen I, Kukk E, Saksela O, Kalkkinen N, Alitalo K | title = A novel vascular endothelial growth factor, VEGF-C, is a ligand for the Flt4 (VEGFR-3) and KDR (VEGFR-2) receptor tyrosine kinases | journal = The EMBO Journal | volume = 15 | issue = 2 | pages = 290–98 | date = Jan 1996 | pmid = 8617204 | pmc = 449944 | doi = 10.1002/j.1460-2075.1996.tb00359.x}}
  • {{cite journal | vauthors = Joukov V, Pajusola K, Kaipainen A, Chilov D, Lahtinen I, Kukk E, Saksela O, Kalkkinen N, Alitalo K | title = A novel vascular endothelial growth factor, VEGF-C, is a ligand for the Flt4 (VEGFR-3) and KDR (VEGFR-2) receptor tyrosine kinases | journal = The EMBO Journal | volume = 15 | issue = 7 | pages = 1751 | date = Apr 1996 | pmid = 8612600 | pmc = 450088 | doi = 10.1002/j.1460-2075.1996.tb00521.x}}
  • {{cite journal | vauthors = Paavonen K, Horelli-Kuitunen N, Chilov D, Kukk E, Pennanen S, Kallioniemi OP, Pajusola K, Olofsson B, Eriksson U, Joukov V, Palotie A, Alitalo K | title = Novel human vascular endothelial growth factor genes VEGF-B and VEGF-C localize to chromosomes 11q13 and 4q34, respectively | journal = Circulation | volume = 93 | issue = 6 | pages = 1079–82 | date = Mar 1996 | pmid = 8653826 | doi = 10.1161/01.cir.93.6.1079 }}
  • {{cite journal | vauthors = Lee J, Gray A, Yuan J, Luoh SM, Avraham H, Wood WI | title = Vascular endothelial growth factor-related protein: a ligand and specific activator of the tyrosine kinase receptor Flt4 | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 93 | issue = 5 | pages = 1988–92 | date = Mar 1996 | pmid = 8700872 | pmc = 39896 | doi = 10.1073/pnas.93.5.1988 }}
  • {{cite journal | vauthors = Joukov V, Sorsa T, Kumar V, Jeltsch M, Claesson-Welsh L, Cao Y, Saksela O, Kalkkinen N, Alitalo K | title = Proteolytic processing regulates receptor specificity and activity of VEGF-C | journal = The EMBO Journal | volume = 16 | issue = 13 | pages = 3898–911 | date = Jul 1997 | pmid = 9233800 | pmc = 1170014 | doi = 10.1093/emboj/16.13.3898 }}
  • {{cite journal | vauthors = Fitz LJ, Morris JC, Towler P, Long A, Burgess P, Greco R, Wang J, Gassaway R, Nickbarg E, Kovacic S, Ciarletta A, Giannotti J, Finnerty H, Zollner R, Beier DR, Leak LV, Turner KJ, Wood CR | title = Characterization of murine Flt4 ligand/VEGF-C | journal = Oncogene | volume = 15 | issue = 5 | pages = 613–8 | date = Jul 1997 | pmid = 9247316 | doi = 10.1038/sj.onc.1201191 }}
  • {{cite journal | vauthors = Dunk C, Ahmed A | title = Expression of VEGF-C and activation of its receptors VEGFR-2 and VEGFR-3 in trophoblast | journal = Histology and Histopathology | volume = 16 | issue = 2 | pages = 359–75 | date = Apr 2001 | pmid = 11332691 | doi = }}
  • {{cite journal | vauthors = Dias S, Choy M, Alitalo K, Rafii S | title = Vascular endothelial growth factor (VEGF)-C signaling through FLT-4 (VEGFR-3) mediates leukemic cell proliferation, survival, and resistance to chemotherapy | journal = Blood | volume = 99 | issue = 6 | pages = 2179–84 | date = Mar 2002 | pmid = 11877295 | doi = 10.1182/blood.V99.6.2179 }}
  • {{cite journal | vauthors = Ueda M, Terai Y, Yamashita Y, Kumagai K, Ueki K, Yamaguchi H, Akise D, Hung YC, Ueki M | title = Correlation between vascular endothelial growth factor-C expression and invasion phenotype in cervical carcinomas | journal = International Journal of Cancer | volume = 98 | issue = 3 | pages = 335–43 | date = Mar 2002 | pmid = 11920583 | doi = 10.1002/ijc.10193 }}
  • {{cite journal | vauthors = Witte D, Thomas A, Ali N, Carlson N, Younes M | title = Expression of the vascular endothelial growth factor receptor-3 (VEGFR-3) and its ligand VEGF-C in human colorectal adenocarcinoma | journal = Anticancer Research | volume = 22 | issue = 3 | pages = 1463–6 | year = 2002 | pmid = 12168824 | doi = }}
  • {{cite journal | vauthors = Schoppmann SF, Birner P, Stöckl J, Kalt R, Ullrich R, Caucig C, Kriehuber E, Nagy K, Alitalo K, Kerjaschki D | title = Tumor-associated macrophages express lymphatic endothelial growth factors and are related to peritumoral lymphangiogenesis | journal = The American Journal of Pathology | volume = 161 | issue = 3 | pages = 947–56 | date = Sep 2002 | pmid = 12213723 | pmc = 1867252 | doi = 10.1016/S0002-9440(10)64255-1 }}
  • {{cite journal | vauthors = Shin HY, Smith ML, Toy KJ, Williams PM, Bizios R, Gerritsen ME | title = VEGF-C mediates cyclic pressure-induced endothelial cell proliferation | journal = Physiological Genomics | volume = 11 | issue = 3 | pages = 245–51 | date = Dec 2002 | pmid = 12388793 | doi = 10.1152/physiolgenomics.00068.2002 }}
  • {{cite journal | vauthors = Yu DH, Wen YM, Sun JD, Wei SL, Xie HP, Pang FH | title = [Relationship among expression of vascular endothelial growth factor-C(VEGF-C), angiogenesis, lymphangiogenesis, and lymphatic metastasis in oral cancer] | journal = AI Zheng = Aizheng = Chinese Journal of Cancer | volume = 21 | issue = 3 | pages = 319–22 | date = Mar 2002 | pmid = 12452004 | doi = }}
  • {{cite journal | vauthors = Nakashima T, Kondoh S, Kitoh H, Ozawa H, Okita S, Harada T, Shiraishi K, Ryozawa S, Okita K | title = Vascular endothelial growth factor-C expression in human gallbladder cancer and its relationship to lymph node metastasis | journal = International Journal of Molecular Medicine | volume = 11 | issue = 1 | pages = 33–9 | date = Jan 2003 | pmid = 12469214 | doi = 10.3892/ijmm.11.1.33 }}
  • {{cite journal | vauthors = Tsai PW, Shiah SG, Lin MT, Wu CW, Kuo ML | title = Up-regulation of vascular endothelial growth factor C in breast cancer cells by heregulin-beta 1. A critical role of p38/nuclear factor-kappa B signaling pathway | journal = The Journal of Biological Chemistry | volume = 278 | issue = 8 | pages = 5750–9 | date = Feb 2003 | pmid = 12471041 | doi = 10.1074/jbc.M204863200 }}
  • {{cite journal | vauthors = Masood R, Kundra A, Zhu S, Xia G, Scalia P, Smith DL, Gill PS | title = Malignant mesothelioma growth inhibition by agents that target the VEGF and VEGF-C autocrine loops | journal = International Journal of Cancer | volume = 104 | issue = 5 | pages = 603–10 | date = May 2003 | pmid = 12594815 | doi = 10.1002/ijc.10996 }}
  • {{cite journal | vauthors = Ohno M, Nakamura T, Kunimoto Y, Nishimura K, Chung-Kang C, Kuroda Y | title = Lymphagenesis correlates with expression of vascular endothelial growth factor-C in colorectal cancer | journal = Oncology Reports | volume = 10 | issue = 4 | pages = 939–43 | year = 2004 | pmid = 12792749 | doi = 10.3892/or.10.4.939 }}
{{refend}}{{Growth factors}}{{Growth factor receptor modulators}}

1 : Genes associated with cancer
随便看

　

开放百科全书收录14589846条英语、德语、日语等多语种百科知识，基本涵盖了大多数领域的百科知识，是一部内容自由、开放的电子版国际百科全书。

　

Copyright © 2023 OENC.NET All Rights Reserved
京ICP备2021023879号 更新时间：2024/11/14 3:16:31