Skip to main content

Lymphangiogenesis: Recapitulation of Angiogensis in Health and Disease

  • Chapter
Book cover New Frontiers in Angiogenesis

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Szuba A, Shin WS, Strauss HW, Rockson S. The third circulation: radionuclide lymphoscintigraphy in the evaluation of lymphedema. J Nucl Med. 2003; 44:43-57.

    PubMed  Google Scholar 

  2. Hong YK, Shin JW, Detmar M. Development of the lymphatic vascular system: a mystery unravels. Dev Dyn. 2004; 231:462-73.

    PubMed  Google Scholar 

  3. Leak LV, Burke JF. Fine structure of the lymphatic capillary and the adjoining connective tissue area. Am J Anat. 1966; 118:785-809.

    PubMed  Google Scholar 

  4. Leak LV. Electron microscopic observations on lymphatic capillaries and the structural components of the connective tissue-lymph interface. Microvasc Res. 1970; 2:361-91.

    PubMed  Google Scholar 

  5. Casley-Smith JR. The fine structure and functioning of tissue channels and lymphatics. Lymphology. 1980; 13:177-83.

    PubMed  Google Scholar 

  6. Barsky SH, Baker A, Siegal GP, Togo S, Liotta LA. Use of anti-basement membrane antibodies to distinguish blood vessel capillaries from lymphatic capillaries. Am J Surg Pathol. 1983; 7:667-77.

    PubMed  Google Scholar 

  7. Ezaki T, Matsuno K, Fujii H, Hayashi N, Miyakawa K, Ohmori J, Kotani M. A new approach for identification of rat lymphatic capillaries using a monoclonal antibody. Arch Histol Cytol. 1990; 53 Suppl:77-86.

    PubMed  Google Scholar 

  8. Oh SJ, Jeltsch MM, Birkenhager R, McCarthy JE, Weich HA, Christ B, Alitalo K, Wilting J. VEGF and VEGF-C: specific induction of angiogenesis and lymphangiogenesis in the differentiated avian chorioallantoic membrane. Dev Biol. 1997; 188:96-109.

    PubMed  Google Scholar 

  9. Lohela M, Saaristo A, Veikkola T, Alitalo K. Lymphangiogenic growth factors, receptors and therapies. Thromb Haemost. 2003; 90:167-84.

    PubMed  Google Scholar 

  10. Olszewski WL. Lymphatics, lymph and lymphoid cells: an integrated immune system. Eur Surg Res. 1986; 18:264-70.

    PubMed  Google Scholar 

  11. Cornford ME, Oldendorf WH. Terminal endothelial cells of lymph capillaries as active transport structures involved in the formation of lymph in rat skin. Lymphology. 1993; 26:67-78.

    PubMed  Google Scholar 

  12. Lubach D, Ludemann W, Berens von Rautenfeld D. Recent findings on the angioarchitecture of the lymph vessel system of human skin. Br J Dermatol. 1996; 135:733-7.

    PubMed  Google Scholar 

  13. Kubik S, Manesta M. Anatomy of the lymph capillaries and precollectors of the skin. In: Bollinger A, Partsch H, Wolfe J, eds. The Initial Lymphatics. Stuttgart, Germany: Thieme-Verlag; 1985:66-74.

    Google Scholar 

  14. Moghimi SM, Bonnemain B. Subcutaneous and intravenous delivery of diagnostic agents to the lymphatic system: applications in lymphoscintigraphy and indirect lymphography. Adv Drug Deliv Rev. 1999; 37:295-312.

    PubMed  Google Scholar 

  15. Nerlich AG, Schleicher E. Identification of lymph and blood capillaries by immunohistochemical staining for various basement membrane components. Histochemistry. 1991; 96:449-53.

    PubMed  Google Scholar 

  16. Pfister G, Saesseli B, Hoffmann U, Geiger M, Bollinger A. Diameters of lymphatic capillaries in patients with different forms of primary lymphedema. Lymphology. 1990; 23:140-4.

    PubMed  Google Scholar 

  17. Ikomi F, Hanna G, Schmid-Schonbein GW. Intracellular and extracellular transport of perfluoro carbon emulsion from subcutaneous tissue to regional lymphatics. Artif Cells Blood Substit Immobil Biotechnol. 1994; 22:1441-7.

    PubMed  Google Scholar 

  18. Ikomi F, Hanna GK, Schmid-Schonbein GW. Mechanism of colloidal particle uptake into the lymphatic system: basic study with percutaneous lymphography. Radiology. 1995; 196:107-13.

    PubMed  Google Scholar 

  19. Ikomi F, Schmid-Schonbein GW. Lymph transport in the skin. Clin Dermatol. 1995; 13:419-27.

    PubMed  Google Scholar 

  20. O’Morchoe PJ, Yang VV, O’Morchoe CC. Lymphatic transport pathways during volume expansion. Microvasc Res. 1980; 20:275-94.

    PubMed  Google Scholar 

  21. Porter CJ, Charman SA. Lymphatic transport of proteins after subcutaneous administration. J Pharm Sci. 2000; 89:297-310.

    PubMed  Google Scholar 

  22. Leak LV. Lymphatic removal of fluids and particles in the mammalian lung. Environ Health Perspect. 1980; 35:55-76.

    PubMed  Google Scholar 

  23. Castenholz A. Structure of initial and collecting lymphatic vessels. In: Olszewski W, ed. Lymph Stasis: Pathophysiology, Diagnosis and Treatment. Boca Raton, FL: CRC Press; 1991:15-41.

    Google Scholar 

  24. Wenzel-Hora BI, Berens von Rautenfeld D, Majewski A, Lubach D, Partsch H. Scanning electron microscopy of the initial lymphatics of the skin after use of the indirect application technique with glutaraldehyde and MERCOX as compared to clinical findings. Lymphology. 1987; 20:126-44.

    PubMed  Google Scholar 

  25. Olszewski W, Machowski Z, Sokolowski J, Wojciechowski J. Alterations in lymphatic vessels in the course of chronic experimental lymphedema. Pol Med J. 1970; 9:1441-8.

    PubMed  Google Scholar 

  26. Schmid-Schonbein GW. Microlymphatics and lymph flow. Physiol Rev. 1990; 70:987-1028.

    PubMed  Google Scholar 

  27. Eisenhoffer J, Kagal A, Klein T, Johnston MG. Importance of valves and lymphangion contractions in determining pressure gradients in isolated lymphatics exposed to elevations in outflow pressure. Microvasc Res. 1995; 49:97-110.

    PubMed  Google Scholar 

  28. Wilting J, Neeff H, Christ B. Embryonic lymphangiogenesis. Cell Tissue Res. 1999; 297:1-11.

    PubMed  Google Scholar 

  29. Cursiefen C, Chen L, Dana MR, Streilein JW. Corneal lymphangiogenesis: evidence, mechanisms, and implications for corneal transplant immunology. Cornea.2003; 22:273-81.

    PubMed  Google Scholar 

  30. Olszewski W. Lymphology and the lymphatic system. In: Olszewski W, ed. Lymph Stasis: Pathophysiology, Diagnosis and Treatment. Boca Raton, FL: CRC Press; 1991:4-12.

    Google Scholar 

  31. Tedder TF, Steeber DA, Chen A, Engel P. The selectins: vascular adhesion molecules. Faseb J. 1995; 9:866-73.

    PubMed  Google Scholar 

  32. Butcher EC, Williams M, Youngman K, Rott L, Briskin M. Lymphocyte trafficking and regional immunity. Adv Immunol. 1999; 72:209-53.

    PubMed  Google Scholar 

  33. Rosen SD. Endothelial ligands for L-selectin: from lymphocyte recirculation to allograft rejection. Am J Pathol. 1999; 155:1013-20.

    PubMed  Google Scholar 

  34. Kunkel EJ, Butcher EC. Chemokines and the tissue-specific migration of lymphocytes. Immunity. 2002; 16:1-4.

    PubMed  Google Scholar 

  35. Gunn MD, Tangemann K, Tam C, Cyster JG, Rosen SD, Williams LT. A chemokine expressed in lymphoid high endothelial venules promotes the adhesion and chemotaxis of naive T lymphocytes. Proc Natl Acad Sci U S A. 1998; 95:258-63.

    PubMed  Google Scholar 

  36. Cyster JG. Chemokines and the homing of dendritic cells to the T cell areas of lymphoid organs. J Exp Med. 1999; 189:447-50.

    PubMed  Google Scholar 

  37. Muller A, Homey B, Soto H, Ge N, Catron D, Buchanan ME, McClanahan T, Murphy E, Yuan W, Wagner SN, Barrera JL, Mohar A, Verastegui E, Zlotnik A. Involvement of chemokine receptors in breast cancer metastasis. Nature. 2001; 410:50-6.

    PubMed  Google Scholar 

  38. Wiley HE, Gonzalez EB, Maki W, Wu MT, Hwang ST. Expression of CC chemokine receptor-7 and regional lymph node metastasis of B16 murine melanoma. J Natl Cancer Inst. 2001; 93:1638-43.

    PubMed  Google Scholar 

  39. Risau W, Flamme I. Vasculogenesis. Annu Rev Cell Dev Biol. 1995; 11:73-91.

    Google Scholar 

  40. Risau W. Mechanisms of angiogenesis. Nature. 1997; 386:671-4.

    PubMed  Google Scholar 

  41. Yancopoulos GD, Klagsbrun M, Folkman J. Vasculogenesis, angiogenesis, and growth factors: ephrins enter the fray at the border. Cell. 1998; 93:661-4.

    PubMed  Google Scholar 

  42. . Asellius G. De lactibus sive lacteis venis. In. Milan: Mediolani; 1627.

    Google Scholar 

  43. Sabin F. On the origin of the lymphatic system from the veins and the development of the lymph hearts and thoracic duct in the pig. Am J Anat. 1902; 1:367-391.

    Google Scholar 

  44. Sabin F. On the development of the superficial lymphatics in the skin of the pig. Am J Anat. 1904; 3:183-195.

    Google Scholar 

  45. Huntington G, McClure CT. he anatomy and development of the jugular lymph sac in the domestic cat (Felis domestica). Anat Rec. 1908; 2:1-19.

    Google Scholar 

  46. Kaipainen A, Korhonen J, Mustonen T, van Hinsbergh VW, Fang GH, Dumont D, Breitman M, Alitalo K. Expression of the fms-like tyrosine kinase 4 gene becomes restricted to lymphatic endothelium during development. Proc Natl Acad Sci U S A. 1995; 92:3566-70.

    PubMed  Google Scholar 

  47. Dumont DJ, Jussila L, Taipale J, Lymboussaki A, Mustonen T, Pajusola K, Breitman M, Alitalo K. Cardiovascular failure in mouse embryos deficient in VEGF receptor-3. Science. 1998; 282:946-9.

    PubMed  Google Scholar 

  48. Wigle JT, Oliver G. Prox1 function is required for the development of the murine lymphatic system. Cell. 1999; 98:769-78.

    PubMed  Google Scholar 

  49. Wigle JT, Harvey N, Detmar M, Lagutina I, Grosveld G, Gunn MD, Jackson DG, Oliver G. An essential role for Prox1 in the induction of the lymphatic endothelial cell phenotype. Embo J. 2002; 21:1505-13.

    PubMed  Google Scholar 

  50. Schneider M, Othman-Hassan K, Christ B, Wilting J. Lymphangioblasts in the avian wing bud. Dev Dyn. 1999; 216:311-9.

    PubMed  Google Scholar 

  51. Papoutsi M, Tomarev SI, Eichmann A, Prols F, Christ B, Wilting J. Endogenous origin of the lymphatics in the avian chorioallantoic membrane. Dev Dyn. 2001; 222:238-51.

    PubMed  Google Scholar 

  52. Wilting J, Papoutsi M, Othman-Hassan K, Rodriguez-Niedenfuhr M, Prols F, Tomarev SI, Eichmann A. Development of the avian lymphatic system. Microsc Res Tech. 2001; 55:81-91.

    PubMed  Google Scholar 

  53. He L, Papoutsi M, Huang R, Tomarev SI, Christ B, Kurz H, Wilting J. Three different fates of cells migrating from somites into the limb bud. Anat Embryol (Berl). 2003; 207:29-34.

    Google Scholar 

  54. Oliver G, Sosa-Pineda B, Geisendorf S, Spana EP, Doe CQ, Gruss P. Prox 1, a prospero-related homeobox gene expressed during mouse development. Mech Dev. 1993; 44:3-16.

    PubMed  Google Scholar 

  55. Tomarev SI, Sundin O, Banerjee-Basu S, Duncan MK, Yang JM, Piatigorsky J. Chicken homeobox gene Prox 1 related to Drosophila prospero is expressed in the developing lens and retina. Dev Dyn. 1996; 206:354-67.

    PubMed  Google Scholar 

  56. Schaefer JJ, Oliver G, Henry JJ. Conservation of gene expression during embryonic lens formation and cornea-lens transdifferentiation in Xenopus laevis. Dev Dyn.1999; 215:308-18.

    PubMed  Google Scholar 

  57. Oliver G, Detmar M. The rediscovery of the lymphatic system: old and new insights into the development and biological function of the lymphatic vasculature. Genes Dev. 2002; 16:773-83.

    PubMed  Google Scholar 

  58. Petrova T, Makinen T, Makela T, Saarela J, Virtanen I, Ferrell R, Finegold D, Kerjaschki D, Yla-Herttuala S, Alitalo K. Lymphatic endothelial reprogramming of vascular endothelial cells by the Prox-1 homeobox transcription factor. EMBO JOURNAL. 2002; 21:4593-4599.

    PubMed  Google Scholar 

  59. Hong Y, Harvey N, Noh Y, Schacht V, Hirakawa S, Detmar M, Oliver G. Prox1 is a master control gene in the program specifying lymphatic endothelial cell fate. Developmental Dynamics. 2002; 225:351-357.

    PubMed  Google Scholar 

  60. Kriehuber E, Breiteneder-Geleff S, Groeger M, Soleiman A, Schoppmann SF, Stingl G, Kerjaschki D, Maurer D. Isolation and characterization of dermal lymphatic and blood endothelial cells reveal stable and functionally specialized cell lineages. J Exp Med. 2001; 194:797-808.

    PubMed  Google Scholar 

  61. Makinen T, Veikkola T, Mustjoki S, Karpanen T, Catimel B, Nice EC, Wise L, Mercer A, Kowalski H, Kerjaschki D, Stacker SA, Achen MG, Alitalo K. Isolated lymphatic endothelial cells transduce growth, survival and migratory signals via the VEGF-C/D receptor VEGFR-3. Embo J. 2001; 20:4762-73.

    PubMed  Google Scholar 

  62. Podgrabinska S, Braun P, Velasco P, Kloos B, Pepper M, Jackson D, M S. Molecular characterization of lymphatic endothelial cells. Proc Natl Acad Sci U S A. 2002; 99:16069-74.

    PubMed  Google Scholar 

  63. Hirakawa S, Hong YK, Harvey N, Schacht V, Matsuda K, Libermann T, Detmar M. Identification of vascular lineage-specific genes by transcriptional profiling of isolated blood vascular and lymphatic endothelial cells. Am J Pathol. 2003; 162:575-86.

    PubMed  Google Scholar 

  64. Huang XZ, Wu JF, Ferrando R, Lee JH, Wang YL, Farese RV, Jr., Sheppard D. Fatal bilateral chylothorax in mice lacking the integrin alpha9beta1. Mol Cell Biol. 2000; 20:5208-15.

    PubMed  Google Scholar 

  65. Wang JF, Zhang XF, Groopman JE. Stimulation of beta 1 integrin induces tyrosine phosphorylation of vascular endothelial growth factor receptor-3 and modulates cell migration. J Biol Chem. 2001; 276:41950-7.

    PubMed  Google Scholar 

  66. Hanahan D, Folkman J. Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell. 1996; 86:353-64.

    PubMed  Google Scholar 

  67. Kerbel RS, Viloria-Petit A, Okada F, Rak J. Establishing a link between oncogenes and tumor angiogenesis. Mol Med. 1998; 4:286-95.

    PubMed  Google Scholar 

  68. Houck KA, Ferrara N, Winer J, Cachianes G, Li B, Leung DW. The vascular endothelial growth factor family: identification of a fourth molecular species and characterization of alternative splicing of RNA. Mol Endocrinol. 1991; 5:1806-14.

    PubMed  Google Scholar 

  69. Tischer E, Mitchell R, Hartman T, Silva M, Gospodarowicz D, Fiddes JC, Abraham JA. The human gene for vascular endothelial growth factor. Multiple protein forms are encoded through alternative exon splicing. J Biol Chem. 1991; 266:11947-54.

    PubMed  Google Scholar 

  70. Poltorak Z, Cohen T, Neufeld G. The VEGF splice variants: properties, receptors, and usage for the treatment of ischemic diseases. Herz. 2000; 25:126-9.

    PubMed  Google Scholar 

  71. Jingjing L, Xue Y, Agarwal N, Roque RS. Human Muller cells express VEGF183, a novel spliced variant of vascular endothelial growth factor. Invest Ophthalmol Vis Sci. 1999; 40:752-9.

    PubMed  Google Scholar 

  72. Soker S, Takashima S, Miao HQ, Neufeld G, Klagsbrun M. Neuropilin-1 is expressed by endothelial and tumor cells as an isoform-specific receptor for vascular endothelial growth factor. Cell. 1998; 92:735-45.

    PubMed  Google Scholar 

  73. Leung DW, Cachianes G, Kuang WJ, Goeddel DV, Ferrara N. Vascular endothelial growth factor is a secreted angiogenic mitogen. Science. 1989; 246:1306-9.

    PubMed  Google Scholar 

  74. Gospodarowicz D, Abraham JA, Schilling J. Isolation and characterization of a vascular endothelial cell mitogen produced by pituitary-derived folliculo stellate cells. Proc Natl Acad Sci U S A. 1989; 86:7311-5.

    PubMed  Google Scholar 

  75. Keck PJ, Hauser SD, Krivi G, Sanzo K, Warren T, Feder J, Connolly DT. Vascular permeability factor, an endothelial cell mitogen related to PDGF. Science.1989; 246:1309-12.

    PubMed  Google Scholar 

  76. Connolly DT, Heuvelman DM, Nelson R, Olander JV, Eppley BL, Delfino JJ, Siegel NR, Leimgruber RM, Feder J. Tumor vascular permeability factor stimulates endothelial cell growth and angiogenesis. J Clin Invest. 1989; 84:1470-8.

    PubMed  Google Scholar 

  77. Ferrara N, Henzel WJ. Pituitary follicular cells secrete a novel heparin-binding growth factor specific for vascular endothelial cells. Biochem Biophys Res Commun. 1989; 161:851-8.

    PubMed  Google Scholar 

  78. Plouet J, Schilling J, Gospodarowicz D. Isolation and characterization of a newly identified endothelial cell mitogen produced by AtT-20 cells. Embo J. 1989; 8:3801-6.

    PubMed  Google Scholar 

  79. Conn G, Bayne ML, Soderman DD, Kwok PW, Sullivan KA, Palisi TM, Hope DA, Thomas KA. Amino acid and cDNA sequences of a vascular endothelial cell mitogen that is homologous to platelet-derived growth factor. Proc Natl Acad Sci U S A. 1990; 87:2628-32.

    PubMed  Google Scholar 

  80. Ferrara N, Davis-Smyth T. The biology of vascular endothelial growth factor. Endocr Rev. 1997; 18:4-25.

    PubMed  Google Scholar 

  81. Weinstein BM. What guides early embryonic blood vessel formation? Dev Dyn. 1999; 215:2-11.

    PubMed  Google Scholar 

  82. Carmeliet P, Ferreira V, Breier G, Pollefeyt S, Kieckens L, Gertsenstein M, Fahrig M, Vandenhoeck A, Harpal K, Eberhardt C, Declercq C, Pawling J, Moons L, Collen D, Risau W, Nagy A. Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele. Nature. 1996; 380:435-9.

    PubMed  Google Scholar 

  83. Ferrara N, Carver-Moore K, Chen H, Dowd M, Lu L, O’Shea KS, Powell-Braxton L, Hillan KJ, Moore MW. Heterozygous embryonic lethality induced by targeted inactivation of the VEGF gene. Nature. 1996; 380:439-42.

    PubMed  Google Scholar 

  84. Alon T, Hemo I, Itin A, Pe’er J, Stone J, Keshet E. Vascular endothelial growth factor acts as a survival factor for newly formed retinal vessels and has implications for retinopathy of prematurity. Nat Med. 1995; 1:1024-8.

    PubMed  Google Scholar 

  85. Yuan F, Chen Y, Dellian M, Safabakhsh N, Ferrara N, Jain RK. Time-dependent vascular regression and permeability changes in established human tumor xenografts induced by an anti-vascular endothelial growth factor/vascular permeability factor antibody. Proc Natl Acad Sci U S A. 1996; 93:14765-70.

    PubMed  Google Scholar 

  86. Benjamin LE, Keshet E. Conditional switching of vascular endothelial growth factor (VEGF) expression in tumors: induction of endothelial cell shedding and regression of hemangioblastoma-like vessels by VEGF withdrawal. Proc Natl Acad Sci U S A. 1997; 94:8761-6.

    PubMed  Google Scholar 

  87. Gerber HP, McMurtrey A, Kowalski J, Yan M, Keyt BA, Dixit V, Ferrara N. Vascular endothelial growth factor regulates endothelial cell survival through the phosphatidylinositol 3’-kinase/Akt signal transduction pathway. Requirement for Flk1/KDR activation. J Biol Chem. 1998; 273:30336-43.

    PubMed  Google Scholar 

  88. Benjamin LE, Hemo I, Keshet E. A plasticity window for blood vessel remodelling is defined by pericyte coverage of the preformed endothelial network and is regulated by PDGF-B and VEGF. Development. 1998; 125:1591-8.

    PubMed  Google Scholar 

  89. Senger DR, Galli SJ, Dvorak AM, Perruzzi CA, Harvey VS, Dvorak HF. Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid. Science. 1983; 219:983-5.

    PubMed  Google Scholar 

  90. Bruce JN, Criscuolo GR, Merrill MJ, Moquin RR, Blacklock JB, Oldfield EH. Vascular permeability induced by protein product of malignant brain tumors: inhibition by dexamethasone. J Neurosurg. 1987; 67:880-4.

    PubMed  Google Scholar 

  91. Dvorak HF, Detmar M, Claffey KP, Nagy JA, van de Water L, Senger DR. Vascular permeability factor/vascular endothelial growth factor: an important mediator of angiogenesis in malignancy and inflammation. Int Arch Allergy Immunol.1995; 107:233-5.

    PubMed  Google Scholar 

  92. Olofsson B, Pajusola K, Kaipainen A, von Euler G, Joukov V, Saksela O, Orpana A, Pettersson RF, Alitalo K, Eriksson U. Vascular endothelial growth factor B, a novel growth factor for endothelial cells. Proc Natl Acad Sci U S A. 1996; 93:2576-81.

    PubMed  Google Scholar 

  93. Makinen T, Olofsson B, Karpanen T, Hellman U, Soker S, Klagsbrun M, Eriksson U, Alitalo K. Differential binding of vascular endothelial growth factor B splice and proteolytic isoforms to neuropilin-1. J Biol Chem. 1999; 274:21217-22.

    PubMed  Google Scholar 

  94. Li X, Aase K, Li H, von Euler G, Eriksson U. Isoform-specific expression of VEGF-B in normal tissues and tumors. Growth Factors. 2001; 19:49-59.

    PubMed  Google Scholar 

  95. Carmeliet P, Moons L, Luttun A, Vincenti V, Compernolle V, De Mol M, Wu Y, Bono F, Devy L, Beck H, Scholz D, Acker T, DiPalma T, Dewerchin M, Noel A, Stalmans I, Barra A, Blacher S, Vandendriessche T, Ponten A, Eriksson U, Plate KH, Foidart JM, Schaper W, Charnock-Jones DS, Hicklin DJ, Herbert JM, Collen D, Persico MG. Synergism between vascular endothelial growth factor and placental growth factor contributes to angiogenesis and plasma extravasation in pathological conditions. Nat Med. 2001; 7:575-83.

    PubMed  Google Scholar 

  96. Carmeliet P, Luttun A. The emerging role of the bone marrow-derived stem cells in (therapeutic) angiogenesis. Thromb Haemost. 2001; 86:289-97.

    PubMed  Google Scholar 

  97. Luttun A, Tjwa M, Moons L, Wu Y, Angelillo-Scherrer A, Liao F, Nagy JA, Hooper A, Priller J, De Klerck B, Compernolle V, Daci E, Bohlen P, Dewerchin M, Herbert JM, Fava R, Matthys P, Carmeliet G, Collen D, Dvorak HF, Hicklin DJ, Carmeliet P. Revascularization of ischemic tissues by PlGF treatment, and inhibition of tumor angiogenesis, arthritis and atherosclerosis by anti-Flt1. Nat Med. 2002; 8:831-40.

    PubMed  Google Scholar 

  98. Hattori K, Heissig B, Wu Y, Dias S, Tejada R, Ferris B, Hicklin DJ, Zhu Z, Bohlen P, Witte L, Hendrikx J, Hackett NR, Crystal RG, Moore MA, Werb Z, Lyden D, Rafii S. Placental growth factor reconstitutes hematopoiesis by recruiting VEGFR1(+) stem cells from bone-marrow microenvironment. Nat Med. 2002; 8:841-9.

    PubMed  Google Scholar 

  99. Maglione D, Guerriero V, Viglietto G, Delli-Bovi P, Persico MG. Isolation of a human placenta cDNA coding for a protein related to the vascular permeability factor. Proc Natl Acad Sci U S A. 1991; 88:9267-71.

    PubMed  Google Scholar 

  100. Park JE, Chen HH, Winer J, Houck KA, Ferrara N. Placenta growth factor. Potentiation of vascular endothelial growth factor bioactivity, in vitro and in vivo, and high affinity binding to Flt-1 but not to Flk-1/KDR. J Biol Chem. 1994; 269:25646-54.

    PubMed  Google Scholar 

  101. Maglione D, Guerriero V, Viglietto G, Ferraro MG, Aprelikova O, Alitalo K, Del Vecchio S, Lei KJ, Chou JY, Persico MG. Two alternative mRNAs coding for the angiogenic factor, placenta growth factor (PlGF), are transcribed from a single gene of chromosome 14. Oncogene. 1993; 8:925-31.

    PubMed  Google Scholar 

  102. Cao Y, Ji WR, Qi P, Rosin A. Placenta growth factor: identification and characterization of a novel isoform generated by RNA alternative splicing. Biochem Biophys Res Commun. 1997; 235:493-8.

    PubMed  Google Scholar 

  103. Migdal M, Huppertz B, Tessler S, Comforti A, Shibuya M, Reich R, Baumann H, Neufeld G. Neuropilin-1 is a placenta growth factor-2 receptor. J Biol Chem. 1998; 273:22272-8.

    PubMed  Google Scholar 

  104. Clauss M, Weich H, Breier G, Knies U, Rockl W, Waltenberger J, Risau W. The vascular endothelial growth factor receptor Flt-1 mediates biological activities. Implications for a functional role of placenta growth factor in monocyte activation and chemotaxis. J Biol Chem. 1996; 271:17629-34.

    PubMed  Google Scholar 

  105. Joukov V, Pajusola K, Kaipainen A, Chilov D, Lahtinen I, Kukk E, Saksela O, Kalkkinen N, Alitalo K. A novel vascular endothelial growth factor, VEGF-C, is a ligand for the Flt4 (VEGFR-3) and KDR (VEGFR-2) receptor tyrosine kinases. Embo J. 1996; 15:1751.

    PubMed  Google Scholar 

  106. Lee J, Gray A, Yuan J, Luoh SM, Avraham H, Wood WI. Vascular endothelial growth factor-related protein: a ligand and specific activator of the tyrosine kinase receptor Flt4. Proc Natl Acad Sci U S A. 1996; 93:1988-92.

    PubMed  Google Scholar 

  107. Orlandini M, Marconcini L, Ferruzzi R, Oliviero S. Identification of a c-fos-induced gene that is related to the platelet-derived growth factor/vascular endothelial growth factor family. Proc Natl Acad Sci U S A. 1996; 93:11675-80.

    PubMed  Google Scholar 

  108. Yamada Y, Nezu J, Shimane M, Hirata Y. Molecular cloning of a novel vascular endothelial growth factor, VEGF-D. Genomics. 1997; 42:483-8.

    PubMed  Google Scholar 

  109. Achen MG, Jeltsch M, Kukk E, Makinen T, Vitali A, Wilks AF, Alitalo K, Stacker SA. Vascular endothelial growth factor D (VEGF-D) is a ligand for the tyrosine kinases VEGF receptor 2 (Flk1) and VEGF receptor 3 (Flt4). Proc Natl Acad Sci U S A. 1998; 95:548-53.

    PubMed  Google Scholar 

  110. Joukov V, Sorsa T, Kumar V, Jeltsch M, Claesson-Welsh L, Cao Y, Saksela O, Kalkkinen N, Alitalo K. Proteolytic processing regulates receptor specificity and activity of VEGF-C. Embo J. 1997; 16:3898-911.

    PubMed  Google Scholar 

  111. Kukk E, Lymboussaki A, Taira S, Kaipainen A, Jeltsch M, Joukov V, Alitalo K. VEGF-C receptor binding and pattern of expression with VEGFR-3 suggests a role in lymphatic vascular development. Development. 1996; 122:3829-37.

    PubMed  Google Scholar 

  112. Eichmann A, Corbel C, Jaffredo T, Breant C, Joukov V, Kumar V, Alitalo K, le Douarin NM. Avian VEGF-C: cloning, embryonic expression pattern and stimulation of the differentiation of VEGFR2-expressing endothelial cell precursors. Development. 1998; 125:743-52.

    PubMed  Google Scholar 

  113. Karkkainen MJ, Haiko P, Sainio K, Partanen J, Taipale J, Petrova TV, Jeltsch M, Jackson DG, Talikka M, Rauvala H, Betsholtz C, Alitalo K. Vascular endothelial growth factor C is required for sprouting of the first lymphatic vessels from embryonic veins. Nat Immunol. 2004; 5:74-80.

    PubMed  Google Scholar 

  114. Partanen TA, Arola J, Saaristo A, Jussila L, Ora A, Miettinen M, Stacker SA, Achen MG, Alitalo K. VEGF-C and VEGF-D expression in neuroendocrine cells and their receptor, VEGFR-3, in fenestrated blood vessels in human tissues. Faseb J. 2000; 14:2087-96.

    PubMed  Google Scholar 

  115. Ristimaki A, Narko K, Enholm B, Joukov V, Alitalo K. Proinflammatory cytokines regulate expression of the lymphatic endothelial mitogen vascular endothelial growth factor-C. J Biol Chem. 1998; 273:8413-8.

    PubMed  Google Scholar 

  116. Skobe M, Brown LF, Tognazzi K, Ganju RK, Dezube BJ, Alitalo K, Detmar M. Vascular endothelial growth factor-C (VEGF-C) and its receptors KDR and flt-4 are expressed in AIDS-associated Kaposi’s sarcoma. J Invest Dermatol. 1999; 113:1047-53.

    PubMed  Google Scholar 

  117. Jeltsch M, Kaipainen A, Joukov V, Meng X, Lakso M, Rauvala H, Swartz M, Fukumura D, Jain RK, Alitalo K. Hyperplasia of lymphatic vessels in VEGF-C transgenic mice. Science. 1997; 276:1423-5.

    PubMed  Google Scholar 

  118. Veikkola T, Jussila L, Makinen T, Karpanen T, Jeltsch M, Petrova TV, Kubo H, Thurston G, McDonald DM, Achen MG, Stacker SA, Alitalo K. Signalling via vascular endothelial growth factor receptor-3 is sufficient for lymphangiogenesis in transgenic mice. Embo J. 2001; 20:1223-31.

    PubMed  Google Scholar 

  119. Makinen T, Jussila L, Veikkola T, Karpanen T, Kettunen MI, Pulkkanen KJ, Kauppinen R, Jackson DG, Kubo H, Nishikawa S, Yla-Herttuala S, Alitalo K. Inhibition of lymphangiogenesis with resulting lymphedema in transgenic mice expressing soluble VEGF receptor-3. Nat Med. 2001; 7:199-205.

    PubMed  Google Scholar 

  120. Cao Y, Linden P, Farnebo J, Cao R, Eriksson A, Kumar V, Qi JH, Claesson-Welsh L, Alitalo K. Vascular endothelial growth factor C induces angiogenesis in vivo. Proc Natl Acad Sci U S A. 1998; 95:14389-94.

    PubMed  Google Scholar 

  121. Witzenbichler B, Maisonpierre PC, Jones P, Yancopoulos GD, Isner JM. Chemotactic properties of angiopoietin-1 and -2, ligands for the endothelial-specific receptor tyrosine kinase Tie2. J Biol Chem. 1998; 273:18514-21.

    PubMed  Google Scholar 

  122. Stacker SA, Stenvers K, Caesar C, Vitali A, Domagala T, Nice E, Roufail S, Simpson RJ, Moritz R, Karpanen T, Alitalo K, Achen MG. Biosynthesis of vascular endothelial growth factor-D involves proteolytic processing which generates non-covalent homodimers. J Biol Chem. 1999; 274:32127-36.

    PubMed  Google Scholar 

  123. Baldwin ME, Roufail S, Halford MM, Alitalo K, Stacker SA, Achen MG. Multiple forms of mouse vascular endothelial growth factor-D are generated by RNA splicing and proteolysis. J Biol Chem. 2001; 276:44307-14.

    PubMed  Google Scholar 

  124. Baldwin ME, Catimel B, Nice EC, Roufail S, Hall NE, Stenvers KL, Karkkainen MJ,Alitalo K, Stacker SA, Achen MG. The specificity of receptor binding by vascular endothelial growth factor-d is different in mouse and man. J Biol Chem.2001; 276:19166-71.

    PubMed  Google Scholar 

  125. Avantaggiato V, Orlandini M, Acampora D, Oliviero S, Simeone A. Embryonic expression pattern of the murine figf gene, a growth factor belonging to platelet-derived growth factor/vascular endothelial growth factor family. Mech Dev. 1998; 73:221-4.

    PubMed  Google Scholar 

  126. Farnebo F, Piehl F, Lagercrantz J. Restricted expression pattern of vegf-d in the adult and fetal mouse: high expression in the embryonic lung. Biochem Biophys Res Commun. 1999; 257:891-4.

    PubMed  Google Scholar 

  127. Marconcini L, Marchio S, Morbidelli L, Cartocci E, Albini A, Ziche M, Bussolino F, Oliviero S. c-fos-induced growth factor/vascular endothelial growth factor D induces angiogenesis in vivo and in vitro. Proc Natl Acad Sci U S A. 1999; 96:9671-6.

    PubMed  Google Scholar 

  128. Neufeld G, Cohen T, Gengrinovitch S, Poltorak Z. Vascular endothelial growth factor (VEGF) and its receptors. Faseb J. 1999; 13:9-22.

    PubMed  Google Scholar 

  129. Karkkainen MJ, Ferrell RE, Lawrence EC, Kimak MA, Levinson KL, McTigue MA, Alitalo K, Finegold DN. Missense mutations interfere with VEGFR-3 signalling in primary lymphoedema. Nat Genet. 2000; 25:153-9.

    PubMed  Google Scholar 

  130. Shibuya M, Yamaguchi S, Yamane A, Ikeda T, Tojo A, Matsushime H, Sato M. Nucleotide sequence and expression of a novel human receptor-type tyrosine kinase gene (flt) closely related to the fms family. Oncogene. 1990; 5:519-24.

    PubMed  Google Scholar 

  131. de Vries C, Escobedo JA, Ueno H, Houck K, Ferrara N, Williams LT. The fms-like tyrosine kinase, a receptor for vascular endothelial growth factor. Science. 1992; 255:989-91.

    PubMed  Google Scholar 

  132. Kendall RL, Thomas KA. Inhibition of vascular endothelial cell growth factor activity by an endogenously encoded soluble receptor. Proc Natl Acad Sci U S A. 1993; 90:10705-9.

    PubMed  Google Scholar 

  133. Gluzman-Poltorak Z, Cohen T, Shibuya M, Neufeld G. Vascular endothelial growth factor receptor-1 and neuropilin-2 form complexes. J Biol Chem. 2001; 276:18688-94.

    PubMed  Google Scholar 

  134. Fong GH, Rossant J, Gertsenstein M, Breitman ML. Role of the Flt-1 receptor tyrosine kinase in regulating the assembly of vascular endothelium. Nature. 1995; 376:66-70.

    PubMed  Google Scholar 

  135. Fong GH, Zhang L, Bryce DM, Peng J. Increased hemangioblast commitment, not vascular disorganization, is the primary defect in flt-1 knock-out mice. Development. 1999; 126:3015-25.

    PubMed  Google Scholar 

  136. Hiratsuka S, Minowa O, Kuno J, Noda T, Shibuya M. Flt-1 lacking the tyrosine kinase domain is sufficient for normal development and angiogenesis in mice. Proc Natl Acad Sci U S A. 1998; 95:9349-54.

    PubMed  Google Scholar 

  137. Hong YK, Lange-Asschenfeldt B, Velasco P, Hirakawa S, Kunstfeld R, Brown LF, Bohlen P, Senger DR, Detmar M. VEGF-A promotes tissue repair-associated lymphatic vessel formation via VEGFR-2 and the alpha1beta1 and alpha2beta1 integrins. Faseb J. 2004; 18:1111-3.

    PubMed  Google Scholar 

  138. Shalaby F, Rossant J, Yamaguchi TP, Gertsenstein M, Wu XF, Breitman ML, Schuh AC. Failure of blood-island formation and vasculogenesis in Flk-1-deficient mice. Nature. 1995; 376:62-6.

    PubMed  Google Scholar 

  139. Shalaby F, Ho J, Stanford WL, Fischer KD, Schuh AC, Schwartz L, Bernstein A, Rossant J. A requirement for Flk1 in primitive and definitive hematopoiesis and vasculogenesis. Cell. 1997; 89:981-90.

    PubMed  Google Scholar 

  140. Ziegler BL, Valtieri M, Porada GA, De Maria R, Muller R, Masella B, Gabbianelli M, Casella I, Pelosi E, Bock T, Zanjani ED, Peschle C. KDR receptor: a key marker defining hematopoietic stem cells. Science. 1999; 285:1553-8.

    PubMed  Google Scholar 

  141. Saaristo A, Veikkola T, Enholm B, Hytonen M, Arola J, Pajusola K, Turunen P, Jeltsch M, Karkkainen MJ, Kerjaschki D, Bueler H, Yla-Herttuala S, Alitalo K. Adenoviral VEGF-C overexpression induces blood vessel enlargement, tortuosity, and leakiness but no sprouting angiogenesis in the skin or mucous membranes. Faseb J. 2002; 16:1041-9.

    PubMed  Google Scholar 

  142. . Matsumoto T, Claesson-Welsh L. VEGF receptor signal transduction. Sci STKE. 2001; 2001:RE21.

    Google Scholar 

  143. Eliceiri BP, Paul R, Schwartzberg PL, Hood JD, Leng J, Cheresh DA. Selective requirement for Src kinases during VEGF-induced angiogenesis and vascular permeability. Mol Cell. 1999; 4:915-24.

    PubMed  Google Scholar 

  144. Paul R, Zhang ZG, Eliceiri BP, Jiang Q, Boccia AD, Zhang RL, Chopp M, Cheresh DA. Src deficiency or blockade of Src activity in mice provides cerebral protection following stroke. Nat Med. 2001; 7:222-7.

    PubMed  Google Scholar 

  145. Nagy JA, Vasile E, Feng D, Sundberg C, Brown LF, Detmar MJ, Lawitts JA, Benjamin L, Tan X, Manseau EJ, Dvorak AM, Dvorak HF. Vascular permeability factor/vascular endothelial growth factor induces lymphangiogenesis as well as angiogenesis. J Exp Med. 2002; 196:1497-506.

    PubMed  Google Scholar 

  146. Enholm B, Karpanen T, Jeltsch M, Kubo H, Stenback F, Prevo R, Jackson DG, Yla-Herttuala S, Alitalo K. Adenoviral expression of vascular endothelial growth factor-C induces lymphangiogenesis in the skin. Circ Res. 2001; 88:623-9.

    PubMed  Google Scholar 

  147. Byzova T, Goldman C, Jankau J, Chen J, Cabrera G, Achen M, Stacker S, Carnevale K, Siemionow M, Deitcher S, DiCorleto P. Adenovirus encoding vascular endothelial growth factor-D induces tissue-specific vascular patterns in vivo. Blood. 2002; 99:4434-42.

    PubMed  Google Scholar 

  148. Kunstfeld R, Hirakawa S, Hong YK, Schacht V, Lange-Asschenfeldt B, Velasco P, Lin C, Fiebiger E, Wei X, Wu Y, Hicklin D, Bohlen P, Detmar M. Induction of cutaneous delayed-type hypersensitivity reactions in VEGF-A transgenic mice results in chronic skin inflammation associated with persistent lymphatic hyperplasia. Blood. 2004; 104:1048-57.

    PubMed  Google Scholar 

  149. Kaipainen A, Korhonen J, Pajusola K, Aprelikova O, Persico MG, Terman BI, Alitalo K. The related FLT4, FLT1, and KDR receptor tyrosine kinases show distinct expression patterns in human fetal endothelial cells. J Exp Med. 1993; 178:2077-88.

    PubMed  Google Scholar 

  150. Pajusola K, Aprelikova O, Armstrong E, Morris S, Alitalo K. Two human FLT4 receptor tyrosine kinase isoforms with distinct carboxy terminal tails are produced by alternative processing of primary transcripts. Oncogene. 1993; 8:2931-7.

    PubMed  Google Scholar 

  151. Pajusola K, Aprelikova O, Korhonen J, Kaipainen A, Pertovaara L, Alitalo R, Alitalo K. FLT4 receptor tyrosine kinase contains seven immunoglobulin-like loops and is expressed in multiple human tissues and cell lines. Cancer Res. 1992; 52:5738-43.

    PubMed  Google Scholar 

  152. Aprelikova O, Pajusola K, Partanen J, Armstrong E, Alitalo R, Bailey SK, McMahon J, Wasmuth J, Huebner K, Alitalo K. FLT4, a novel class III receptor tyrosine kinase in chromosome 5q33-qter. Cancer Res. 1992; 52:746-8.

    PubMed  Google Scholar 

  153. Galland F, Karamysheva A, Pebusque MJ, Borg JP, Rottapel R, Dubreuil P, Rosnet O, Birnbaum D. The FLT4 gene encodes a transmembrane tyrosine kinase related to the vascular endothelial growth factor receptor. Oncogene. 1993; 8:1233-40.

    PubMed  Google Scholar 

  154. Ferrell R. Research perspectives in inherited lymphatic disease. Ann N Y Acad Sci. 2002; 979:39-51.

    PubMed  Google Scholar 

  155. Joukov V, Kumar V, Sorsa T, Arighi E, Weich H, Saksela O, Alitalo K. A recombinant mutant vascular endothelial growth factor-C that has lost vascular endothelial growth factor receptor-2 binding, activation, and vascular permeability activities. J Biol Chem. 1998; 273:6599-602.

    PubMed  Google Scholar 

  156. Yancopoulos GD, Davis S, Gale NW, Rudge JS, Wiegand SJ, Holash J. Vascular-specific growth factors and blood vessel formation. Nature. 2000; 407:242-8.

    PubMed  Google Scholar 

  157. Jones N, Iljin K, Dumont DJ, Alitalo K. Tie receptors: new modulators of angiogenic and lymphangiogenic responses. Nat Rev Mol Cell Biol. 2001; 2:257-67.

    PubMed  Google Scholar 

  158. Loughna S, Sato TN. Angiopoietin and Tie signaling pathways in vascular development. Matrix Biol. 2001; 20:319-25.

    PubMed  Google Scholar 

  159. Iljin K, Petrova TV, Veikkola T, Kumar V, Poutanen M, Alitalo K. A fluorescent Tie1 reporter allows monitoring of vascular development and endothelial cell isolation from transgenic mouse embryos. Faseb J. 2002; 16:1764-74.

    PubMed  Google Scholar 

  160. Sato TN, Tozawa Y, Deutsch U, Wolburg-Buchholz K, Fujiwara Y, Gendron-Maguire M, Gridley T, Wolburg H, Risau W, Qin Y. Distinct roles of the receptor tyrosine kinases Tie-1 and Tie-2 in blood vessel formation. Nature. 1995; 376:70-4.

    PubMed  Google Scholar 

  161. Puri MC, Rossant J, Alitalo K, Bernstein A, Partanen J. The receptor tyrosine kinase TIE is required for integrity and survival of vascular endothelial cells. Embo J. 1995; 14:5884-91.

    PubMed  Google Scholar 

  162. Dumont DJ, Gradwohl G, Fong GH, Puri MC, Gertsenstein M, Auerbach A, Breitman ML. Dominant-negative and targeted null mutations in the endothelial receptor tyrosine kinase, tek, reveal a critical role in vasculogenesis of the embryo. Genes Dev. 1994; 8:1897-909.

    PubMed  Google Scholar 

  163. Davis S, Aldrich TH, Jones PF, Acheson A, Compton DL, Jain V, Ryan TE, Bruno J, Radziejewski C, Maisonpierre PC, Yancopoulos GD. Isolation of angiopoietin-1, a ligand for the TIE2 receptor, by secretion-trap expression cloning. Cell.1996; 87: 1161-9.

    PubMed  Google Scholar 

  164. Maisonpierre PC, Suri C, Jones PF, Bartunkova S, Wiegand SJ, Radziejewski C, Compton D, McClain J, Aldrich TH, Papadopoulos N, Daly TJ, Davis S, Sato TN, Yancopoulos GD. Angiopoietin-2, a natural antagonist for Tie2 that disrupts in vivo angiogenesis. Science. 1997; 277:55-60.

    PubMed  Google Scholar 

  165. Kim I, Kwak HJ, Ahn JE, So JN, Liu M, Koh KN, Koh GY. Molecular cloning and characterization of a novel angiopoietin family protein, angiopoietin-3. FEBS Lett. 1999; 443:353-6.

    PubMed  Google Scholar 

  166. Valenzuela DM, Griffiths JA, Rojas J, Aldrich TH, Jones PF, Zhou H, McClain J, Copeland NG, Gilbert DJ, Jenkins NA, Huang T, Papadopoulos N, Maisonpierre PC, Davis S, Yancopoulos GD. Angiopoietins 3 and 4: diverging gene counterparts in mice and humans. Proc Natl Acad Sci U S A. 1999; 96:1904-9.

    PubMed  Google Scholar 

  167. Suri C, Jones PF, Patan S, Bartunkova S, Maisonpierre PC, Davis S, Sato TN, Yancopoulos GD. Requisite role of angiopoietin-1, a ligand for the TIE2 receptor, during embryonic angiogenesis. Cell. 1996; 87:1171-80.

    PubMed  Google Scholar 

  168. Thurston G, Rudge JS, Ioffe E, Zhou H, Ross L, Croll SD, Glazer N, Holash J, McDonald DM, Yancopoulos GD. Angiopoietin-1 protects the adult vasculature against plasma leakage. Nat Med. 2000; 6:460-3.

    PubMed  Google Scholar 

  169. Mandriota SJ, Pepper MS. Regulation of angiopoietin-2 mRNA levels in bovine microvascular endothelial cells by cytokines and hypoxia. Circ Res. 1998; 83:852-9.

    PubMed  Google Scholar 

  170. Mandriota SJ, Pyke C, Di Sanza C, Quinodoz P, Pittet B, Pepper MS. Hypoxia-inducible angiopoietin-2 expression is mimicked by iodonium compounds and occurs in the rat brain and skin in response to systemic hypoxia and tissue ischemia. Am J Pathol. 2000; 156:2077-89.

    PubMed  Google Scholar 

  171. Holash J, Maisonpierre PC, Compton D, Boland P, Alexander CR, Zagzag D, Yancopoulos GD, Wiegand SJ. Vessel cooption, regression, and growth in tumors mediated by angiopoietins and VEGF. Science. 1999; 284:1994-8.

    PubMed  Google Scholar 

  172. Holash J, Wiegand SJ, Yancopoulos GD. New model of tumor angiogenesis: dynamic balance between vessel regression and growth mediated by angiopoietins and VEGF. Oncogene. 1999; 18:5356-62.

    PubMed  Google Scholar 

  173. Gale NW, Thurston G, Hackett SF, Renard R, Wang Q, McClain J, Martin C, Witte C, Witte MH, Jackson D, Suri C, Campochiaro PA, Wiegand SJ, Yancopoulos GD. Angiopoietin-2 is required for postnatal angiogenesis and lymphatic patterning, and only the latter role is rescued by Angiopoietin-1. Dev Cell. 2002; 3:411-23.

    PubMed  Google Scholar 

  174. Banerji S, Ni J, Wang SX, Clasper S, Su J, Tammi R, Jones M, Jackson DG. LYVE-1, a new homologue of the CD44 glycoprotein, is a lymph-specific receptor for hyaluronan. J Cell Biol. 1999; 144:789-801.

    PubMed  Google Scholar 

  175. Jackson DG, Prevo R, Clasper S, Banerji S. LYVE-1, the lymphatic system and tumor lymphangiogenesis. Trends Immunol. 2001; 22:317-21.

    PubMed  Google Scholar 

  176. Jackson DG. The lymphatics revisited: new perspectives from the hyaluronan receptor LYVE-1. Trends Cardiovasc Med. 2003; 13:1-7.

    PubMed  Google Scholar 

  177. Wetterwald A, Hoffstetter W, Cecchini MG, Lanske B, Wagner C, Fleisch H, Atkinson M. Characterization and cloning of the E11 antigen, a marker expressed by rat osteoblasts and osteocytes. Bone. 1996; 18:125-32.

    PubMed  Google Scholar 

  178. Schacht V, Ramirez MI, Hong YK, Hirakawa S, Feng D, Harvey N, Williams M, Dvorak AM, Dvorak HF, Oliver G, Detmar M. T1alpha/podoplanin deficiency disrupts normal lymphatic vasculature formation and causes lymphedema. Embo J. 2003; 22:3546-56.

    PubMed  Google Scholar 

  179. Ramirez MI, Millien G, Hinds A, Cao Y, Seldin DC, Williams MC. T1alpha, a lung type I cell differentiation gene, is required for normal lung cell proliferation and alveolus formation at birth. Dev Biol. 2003; 256:61-72.

    PubMed  Google Scholar 

  180. Rishi AK, Joyce-Brady M, Fisher J, Dobbs LG, Floros J, VanderSpek J, Brody JS, Williams MC. Cloning, characterization, and development expression of a rat lung alveolar type I cell gene in embryonic endodermal and neural derivatives. Dev Biol. 1995; 167:294-306.

    PubMed  Google Scholar 

  181. Hong YK, Detmar M. Prox1, master regulator of the lymphatic vasculature phenotype. Cell Tissue Res. 2003; 314:85-92.

    PubMed  Google Scholar 

  182. Neufeld G, Cohen T, Shraga N, Lange T, Kessler O, Herzog Y. The neuropilins: multifunctional semaphorin and VEGF receptors that modulate axon guidance and angiogenesis. Trends Cardiovasc Med. 2002; 12:13-9.

    PubMed  Google Scholar 

  183. Giraudo E, Primo L, Audero E, Gerber HP, Koolwijk P, Soker S, Klagsbrun M, Ferrara N, Bussolino F. Tumor necrosis factor-alpha regulates expression of vascular endothelial growth factor receptor-2 and of its co-receptor neuropilin-1 in human vascular endothelial cells. J Biol Chem. 1998; 273: 22128-35.

    PubMed  Google Scholar 

  184. Arruda VR, Hagstrom JN, Deitch J, Heiman-Patterson T, Camire RM, Chu K, Fields PA, Herzog RW, Couto LB, Larson PJ, High KA. Posttranslational modifications of recombinant myotube-synthesized human factor IX. Blood. 2001; 97:130-8.

    PubMed  Google Scholar 

  185. 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. A model for gene therapy of human hereditary lymphedema. Proc Natl Acad Sci U S A. 2001; 98:12677-82.

    PubMed  Google Scholar 

  186. Paavonen K, Puolakkainen P, Jussila L, Jahkola T, Alitalo K. Vascular endothelial growth factor receptor-3 in lymphangiogenesis in wound healing. Am J Pathol. 2000; 156:1499-504.

    PubMed  Google Scholar 

  187. Clark E, Clark E. Observations on the new growth of lymphatic vessels as seen in transparent chambers introduced into the rabbit’s ear. Am J Anat. 1932; 51:43-87.

    Google Scholar 

  188. Rockson S. Primary Lymphedema. In: Ernst C, Stanley J, eds. Current Therapy in Vascular Surgery. Fourth ed. Philadelphia: Mosby; 2000:915-918.

    Google Scholar 

  189. Witte M, Way D, Witte C, Bernas MLM, significance and clinical implications. In: Goldberg ID, Rosen EM, editors. Regulation of angiogenesis. Basel, Switzerland: Birkhauser Verlag; 1997. 65-112. Lymphangiogenesis: Mechanisms, significance and clinical implications. In: Goldberg I, Rosen E, eds. Regulation of angiogenesis. Basel, Switzerland: Birkhauser Verlag; 1997:65-112.

    Google Scholar 

  190. Karpanen T, Alitalo K. Lymphatic vessels as targets of tumor therapy? J Exp Med. 2001; 194:F37-42.

    PubMed  Google Scholar 

  191. Rockson SG. Lymphedema. Am J Med. 2001; 110:288-95.

    Google Scholar 

  192. Szuba A, Rockson SG. Lymphedema: classification, diagnosis and therapy. Vasc Med. 1998; 3:145-56.

    PubMed  Google Scholar 

  193. Shin WS, Szuba A, Rockson SG. Animal models for the study of lymphatic insufficiency. Lymphat Res Biol. 2003; 1:159-69.

    PubMed  Google Scholar 

  194. Piller NB. Lymphoedema, macrophages and benzopyrones. Lymphology. 1980; 13: 109-19.

    PubMed  Google Scholar 

  195. Piller NB. Macrophage and tissue changes in the developmental phases of secondary lymphoedema and during conservative therapy with benzopyrone. Arch Histol Cytol. 1990; 53:209-18.

    PubMed  Google Scholar 

  196. Szuba A, Skobe M, Karkkainen MJ, Shin WS, Beynet DP, Rockson NB, Dakhil N, Spilman S, Goris ML, Strauss HW, Quertermous T, Alitalo K, Rockson SG. Therapeutic lymphangiogenesis with human recombinant VEGF-C. FASEB J. 2002; 16 (14): 1985-1987.

    PubMed  Google Scholar 

  197. Velanovich V, Szymanski W. Quality of life of breast cancer patients with lymphedema. Am J Surg. 1999; 177:184-7; discussion 188.

    PubMed  Google Scholar 

  198. Tobin MB, Lacey HJ, Meyer L, Mortimer PS. The psychological morbidity of breast cancer-related arm swelling. Psychological morbidity of lymphoedema. Cancer. 1993; 72:3248-52.

    PubMed  Google Scholar 

  199. Maunsell E, Brisson J, Deschenes L. Arm problems and psychological distress after surgery for breast cancer. Can J Surg. 1993; 36:315-20.

    PubMed  Google Scholar 

  200. Passik S, Newman M, Brennan M, Tunkel R. Predictors of psychological distress, sexual dysfunction and physical functioning among women with upper extremity lymphedema related to breast cancer. Psycho-Oncology. 1995; 4:255-263.

    Google Scholar 

  201. Rockson SG. Lymphedema after surgery for cancer: the role of patient support groups in patient therapy. Disease Management and Health Outcomes. 2002; 10:345-7.

    Google Scholar 

  202. Rockson SG, Miller LT, Senie R, Brennan MJ, Casley-Smith JR, Foldi E, Foldi M, Gamble GL, Kasseroller RG, Leduc A, Lerner R, Mortimer PS, Norman SA, Plotkin CL, Rinehart-Ayres ME, Walder AL. American Cancer Society Lymphedema Workshop. Workgroup III: Diagnosis and management of lymphedema. Cancer. 1998; 83:2882-5.

    PubMed  Google Scholar 

  203. Rivard A, Isner JM. Angiogenesis and vasculogenesis in treatment of cardiovascular disease. Mol Med. 1998; 4:429-40.

    PubMed  Google Scholar 

  204. Baumgartner I, Pieczek A, Manor O, Blair R, Kearney M, Walsh K, Isner JM. Constitutive expression of phVEGF165 after intramuscular gene transfer promotes collateral vessel development in patients with critical limb ischemia [see comments]. Circulation. 1998; 97:1114-23.

    PubMed  Google Scholar 

  205. Ferrara N, Alitalo K. Clinical applications of angiogenic growth factors and their inhibitors. Nat Med. 1999; 5:1359-64.

    PubMed  Google Scholar 

  206. Ferrell RE, Levinson KL, Esman JH, Kimak MA, Lawrence EC, Barmada MM, Finegold DN. Hereditary lymphedema: evidence for linkage and genetic heterogeneity. Hum Mol Genet. 1998; 7:2073-8.

    PubMed  Google Scholar 

  207. Evans AL, Brice G, Sotirova V, Mortimer P, Beninson J, Burnand K, Rosbotham J, Child A, Sarfarazi M. Mapping of primary congenital lymphedema to the 5q35.3 region. Am J Hum Genet. 1999; 64:547-55.

    PubMed  Google Scholar 

  208. Witte MH, Erickson R, Bernas M, Andrade M, Reiser F, Conlon W, Hoyme HE, Witte CL. Phenotypic and genotypic heterogeneity in familial Milroy lymphedema. Lymphology. 1998; 31:145-55.

    PubMed  Google Scholar 

  209. Karkkainen MJ, Petrova TV. Vascular endothelial growth factor receptors in the regulation of angiogenesis and lymphangiogenesis. Oncogene. 2000; 19:5598-605.

    PubMed  Google Scholar 

  210. Karkkainen MJ, Jussila L, Ferrell RE, Finegold DN, Alitalo K. Molecular regulation of lymphangiogenesis and targets for tissue oedema. Trends Mol Med. 2001; 7:18-22.

    PubMed  Google Scholar 

  211. Barber JC, Temple IK, Campbell PL, Collinson MN, Campbell CM, Renshaw RM, Dennis NR. Unbalanced translocation in a mother and her son in one of two 5;10 translocation families. Am J Med Genet. 1996; 62:84-90.

    PubMed  Google Scholar 

  212. Groen SE, Drewes JG, de Boer EG, Hoovers JM, Hennekam RC. Repeated unbalanced offspring due to a familial translocation involving chromosomes 5 and 6. Am J Med Genet. 1998; 80:448-53.

    PubMed  Google Scholar 

  213. Fang J, Dagenais SL, Erickson RP, Arlt MF, Glynn MW, Gorski JL, Seaver LH, Glover TW. Mutations in FOXC2 (MFH-1), a forkhead family transcription factor, are responsible for the hereditary lymphedema-distichiasis syndrome [In Process Citation]. Am J Hum Genet. 2000; 67:1382-8.

    PubMed  Google Scholar 

  214. Dale RF. Primary lymphoedema when found with distichiasis is of the type defined as bilateral hyperplasia by lymphography. J Med Genet. 1987; 24:170-1.

    PubMed  Google Scholar 

  215. Falls HF, Kertesz ED. A New Syndrome Combining Pterygium Colli with Developmental Anomalies of the Eyelids and Lymphatics of the Lower Extremities. Trans Am Ophthalmol Soc. 1964; 62:248-75.

    PubMed  Google Scholar 

  216. Chynn KY. Congenital spinal extradural cyst in two siblings. Am J Roentgenol Radium Ther Nucl Med. 1967; 101:204-15.

    PubMed  Google Scholar 

  217. Pap Z, Biro T, Szabo L, Papp Z. Syndrome of lymphoedema and distichiasis. Hum Genet. 1980; 53:309-10.

    PubMed  Google Scholar 

  218. Corbett CR, Dale RF, Coltart DJ, Kinmonth JB. Congenital heart disease in patients with primary lymphedemas. Lymphology. 1982; 15:85-90.

    PubMed  Google Scholar 

  219. Goldstein S, Qazi QH, Fitzgerald J, Goldstein J, Friedman AP, Sawyer P. Distichiasis, congenital heart defects and mixed peripheral vascular anomalies. Am J Med Genet. 1985; 20:283-94.

    PubMed  Google Scholar 

  220. Bartley GB, Jackson IT. Distichiasis and cleft palate. Plast Reconstr Surg.1989; 84:129-32.

    PubMed  Google Scholar 

  221. Mangion J, Rahman N, Mansour S, Brice G, Rosbotham J, Child AH, Murday VA, Mortimer PS, Barfoot R, Sigurdsson A, Edkins S, Sarfarazi M, Burnand K, Evans AL, Nunan TO, Stratton MR, Jeffery S. A gene for lymphedema-distichiasis maps to 16q24.3. Am J Hum Genet. 1999; 65:427-32.

    PubMed  Google Scholar 

  222. Bell R, Brice G, Child AH, Murday VA, Mansour S, Sandy CJ, Collin JR, Mortimer P, Callen DF, Burnand K. Reduction of the genetic interval for lyphoedema-distichiasis to below 2 Mb. J Med Genet. 2000; 37:725.

    PubMed  Google Scholar 

  223. Finegold DN, Kimak MA, Lawrence EC, Levinson KL, Cherniske EM, Pober BR, Dunlap JW, Ferrell RE. Truncating mutations in FOXC2 cause multiple lymphedema syndromes. Hum Mol Genet. 2001; 10:1185-9.

    PubMed  Google Scholar 

  224. Erickson RP, Dagenais SL, Caulder MS, Downs CA, Herman G, Jones MC, Kerstjens-Frederikse WS, Lidral AC, McDonald M, Nelson CC, Witte M, Glover TW. Clinical heterogeneity in lymphoedema-distichiasis with FOXC2 truncating mutations. J Med Genet. 2001; 38:761-6.

    PubMed  Google Scholar 

  225. Bell R, Brice G, Child AH, Murday VA, Mansour S, Sandy CJ, Collin JR, Brady AF, Callen DF, Burnand K, Mortimer P, Jeffery S. Analysis of lymphoedema-distichiasis families for FOXC2 mutations reveals small insertions and deletions throughout the gene. Hum Genet. 2001; 108:546-51.

    PubMed  Google Scholar 

  226. Weigel D, Jurgens G, Kuttner F, Seifert E, Jackle H. The homeotic gene fork head encodes a nuclear protein and is expressed in the terminal regions of the Drosophila embryo. Cell. 1989; 57:645-58.

    PubMed  Google Scholar 

  227. Winnier GE, Hargett L, Hogan BL. The winged helix transcription factor MFH1 is required for proliferation and patterning of paraxial mesoderm in the mouse embryo. Genes Dev. 1997; 11:926-40.

    PubMed  Google Scholar 

  228. Iida K, Koseki H, Kakinuma H, Kato N, Mizutani-Koseki Y, Ohuchi H, Yoshioka H, Noji S, Kawamura K, Kataoka Y, Ueno F, Taniguchi M, Yoshida N, Sugiyama T, Miura N. Essential roles of the winged helix transcription factor MFH-1 in aortic arch patterning and skeletogenesis. Development. 1997; 124:4627-38.

    PubMed  Google Scholar 

  229. Smith RS, Zabaleta A, Kume T, Savinova OV, Kidson SH, Martin JE, Nishimura DY, Alward WL, Hogan BL, John SW. Haploinsufficiency of the transcription factors FOXC1 and FOXC2 results in aberrant ocular development. Hum Mol Genet. 2000; 9:1021-32.

    PubMed  Google Scholar 

  230. Olszewski W, Machowski Z, Sokolowski J, Nielubowicz J. Experimental lymphedema in dogs. J Cardiovasc Surg (Torino). 1968; 9:178-83.

    Google Scholar 

  231. Rockson SG. Preclinical models of lymphatic disease: the potential for growth factor and gene therapy. Ann N Y Acad Sci. 2002; 979:64-75; discussion 76-9.

    PubMed  Google Scholar 

  232. Wang GY, Zhong SZ. A model of experimental lymphedema in rats’ limbs. Microsurgery. 1985; 6:204-10.

    PubMed  Google Scholar 

  233. Slavin SA, Van den Abbeele AD, Losken A, Swartz MA, Jain RK. Return of lymphatic function after flap transfer for acute lymphedema. Ann Surg. 1999; 229:421-7.

    PubMed  Google Scholar 

  234. Swartz MA, Berk DA, Jain RK. Transport in lymphatic capillaries. I. Macroscopic measurements using residence time distribution theory. Am J Physiol. 1996; 270: H324-9.

    PubMed  Google Scholar 

  235. Kriederman B, Myloyde T, Bernas M, Lee-Donaldson L, Preciado S, Lynch M, Stea B, Summers P, Witte C, Witte M. Limb volume reduction after physical treatment by compression and/or massage in a rodent model of peripheral lymphedema. Lymphology. 2002; 35:23-7.

    PubMed  Google Scholar 

  236. Lee-Donaldson L, Witte MH, Bernas M, Witte CL, Way D, Stea B. Refinement of a rodent model of peripheral lymphedema. Lymphology. 1999; 32:111-7.

    PubMed  Google Scholar 

  237. Gray H. Studies of the regeneration of lymphatic vessels. J Anat. 1939;74:309.

    Google Scholar 

  238. Goffrini P, Bobbio P. [the Lymph Circulation of the Upper Extremity Following the Radical Operation of Mammary Cancer and Its Relations to the Secondary Edema of the Arm.]. Chirurg. 1964; 35:145-8.

    PubMed  Google Scholar 

  239. Huang GK, Hsin YP. An experimental model for lymphedema in rabbit ear. Microsurgery. 1983; 4:236-42.

    PubMed  Google Scholar 

  240. Blau HM, Banfi A. The well-tempered vessel. Nat Med. 2001; 7:532-4.

    PubMed  Google Scholar 

  241. Yla-Herttuala S. Gene therapy for coronary heart disease. J Intern Med. 2001; 250: 367-8.

    PubMed  Google Scholar 

  242. Isner JM. Myocardial gene therapy. Nature. 2002; 415:234-9.

    PubMed  Google Scholar 

  243. Yla-Herttuala S, Alitalo K. Gene transfer as a tool to induce therapeutic vascular growth. Nat Med. 2003; 9:694-701.

    PubMed  Google Scholar 

  244. 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. Vascular endothelial growth factor-C-mediated lymphangiogenesis promotes tumour metastasis. Embo J. 2001; 20:672-82.

    PubMed  Google Scholar 

  245. Skobe M, Hawighorst T, Jackson DG, Prevo R, Janes L, Velasco P, Riccardi L, Alitalo K, Claffey K, Detmar M. Induction of tumor lymphangiogenesis by VEGF-C promotes breast cancer metastasis. Nat Med. 2001; 7:192-8.

    PubMed  Google Scholar 

  246. Stacker SA, Caesar C, Baldwin ME, Thornton GE, Williams RA, Prevo R, Jackson DG, Nishikawa S, Kubo H, Achen MG. VEGF-D promotes the metastatic spread of tumor cells via the lymphatics. Nat Med. 2001; 7:186-91.

    PubMed  Google Scholar 

  247. Karpanen T, Egeblad M, Karkkainen MJ, Kubo H, Yla-Herttuala S, Jaattela M, Alitalo K. Vascular endothelial growth factor C promotes tumor lymphangiogenesis and intralymphatic tumor growth. Cancer Res. 2001; 61:1786-90.

    PubMed  Google Scholar 

  248. He Y, Kozaki K, Karpanen T, Koshikawa K, Yla-Herttuala S, Takahashi T, Alitalo K. Suppression of tumor lymphangiogenesis and lymph node metastasis by blocking vascular endothelial growth factor receptor3 signaling. J Natl Cancer Inst.2002; 94:819-25.

    PubMed  Google Scholar 

  249. Mattila MM, Ruohola JK, Karpanen T, Jackson DG, Alitalo K, Harkonen PL. VEGF-C induced lymphangiogenesis is associated with lymph node metastasis in orthotopic MCF-7 tumors. Int J Cancer. 2002; 98:946-51.

    PubMed  Google Scholar 

  250. Saaristo A, Karkkainen MJ, Alitalo K. Insights into the molecular pathogenesis and targeted treatment of lymphedema. Ann N Y Acad Sci. 2002; 979:94-110.

    PubMed  Google Scholar 

  251. Daly TM, Ohlemiller KK, Roberts MS, Vogler CA, Sands MS. Prevention of systemic clinical disease in MPS VII mice following AAV-mediated neonatal gene transfer. Gene Ther. 2001; 8:1291-8.

    PubMed  Google Scholar 

  252. Monahan PE, Samulski RJ. Adeno-associated virus vectors for gene therapy: more pros than cons? Mol Med Today. 2000; 6:433-40.

    PubMed  Google Scholar 

  253. Saaristo A, Veikkola T, Tammela T, Enholm B, Karkkainen MJ, Pajusola K, Bueler H, Yla-Herttuala S, Alitalo K. Lymphangiogenic gene therapy with minimal blood vascular side effects. J Exp Med. 2002; 196:719-30.

    PubMed  Google Scholar 

  254. Carmeliet P. VEGF gene therapy: stimulating angiogenesis or angioma-genesis? Nat Med. 2000; 6:1102-3.

    PubMed  Google Scholar 

  255. Epstein SE, Kornowski R, Fuchs S, Dvorak HF. Angiogenesis therapy: amidst the hype, the neglected potential for serious side effects. Circulation. 2001; 104:115-9.

    PubMed  Google Scholar 

  256. Thurston G, Suri C, Smith K, McClain J, Sato TN, Yancopoulos GD, McDonald DM. Leakage-resistant blood vessels in mice transgenically overexpressing angiopoietin-1. Science. 1999; 286:2511-4.

    PubMed  Google Scholar 

  257. Witzenbichler B, Asahara T, Murohara T, Silver M, Spyridopoulos I, Magner M, Principe N, Kearney M, Hu JS, Isner JM. Vascular endothelial growth factor-C (VEGFC/VEGF-2) promotes angiogenesis in the setting of tissue ischemia. Am J Pathol. 1998; 153:381-94.

    PubMed  Google Scholar 

  258. Suri C, McClain J, Thurston G, McDonald DM, Zhou H, Oldmixon EH, Sato TN, Yancopoulos GD. Increased vascularization in mice overexpressing angiopoietin-1. Science. 1998; 282:468-71.

    PubMed  Google Scholar 

  259. Liotta LA, Stetler-Stevenson WG, Steeg PS. Cancer invasion and metastasis: positive and negative regulatory elements. Cancer Invest. 1991; 9:543-51.

    PubMed  Google Scholar 

  260. Cassella M, Skobe M. Lymphatic vessel activation in cancer. Ann N Y Acad Sci. 2002; 979:120-30.

    PubMed  Google Scholar 

  261. Zetter BR. Adhesion molecules in tumor metastasis. Semin Cancer Biol. 1993; 4: 219-29.

    PubMed  Google Scholar 

  262. Padera TP, Kadambi A, di Tomaso E, Carreira CM, Brown EB, Boucher Y, Choi NC, Mathisen D, Wain J, Mark EJ, Munn LL, Jain RK. Lymphatic metastasis in the absence of functional intratumor lymphatics. Science. 2002; 296:1883-6.

    PubMed  Google Scholar 

  263. Skobe M, Hamberg LM, Hawighorst T, Schirner M, Wolf GL, Alitalo K, Detmar M. Concurrent induction of lymphangiogenesis, angiogenesis, and macrophage recruitment by vascular endothelial growth factor-C in melanoma. Am J Pathol. 2001; 159:893-903.

    PubMed  Google Scholar 

  264. Birner P, Schindl M, Obermair A, Plank C, Breitenecker G, Kowalski H, Oberhuber G. Lymphatic microvessel density in epithelial ovarian cancer: its impact on prognosis. Anticancer Res. 2000; 20:2981-5.

    PubMed  Google Scholar 

  265. Birner P, Schindl M, Obermair A, Breitenecker G, Kowalski H, Oberhuber G. Lymphatic microvessel density as a novel prognostic factor in early-stage invasive cervical cancer. Int J Cancer. 2001; 95:29-33.

    PubMed  Google Scholar 

  266. de Waal RM, van Altena MC, Erhard H, Weidle UH, Nooijen PT, Ruiter DJ. Lack of lymphangiogenesis in human primary cutaneous melanoma. Consequences for the mechanism of lymphatic dissemination. Am J Pathol. 1997; 150:1951-7.

    PubMed  Google Scholar 

  267. Clarijs R, Schalkwijk L, Ruiter DJ, de Waal RM. Lack of lymphangiogenesis despite coexpression of VEGF-C and its receptor Flt-4 in uveal melanoma. Invest Ophthalmol Vis Sci. 2001; 42:1422-8.

    PubMed  Google Scholar 

  268. Mouta Carreira C, Nasser SM, di Tomaso E, Padera TP, Boucher Y, Tomarev SI, Jain RK. LYVE-1 is not restricted to the lymph vessels: expression in normal liver blood sinusoids and down-regulation in human liver cancer and cirrhosis. Cancer Res. 2001; 61:8079-84.

    PubMed  Google Scholar 

  269. Papoutsi M, Siemeister G, Weindel K, Tomarev SI, Kurz H, Schachtele C, Martiny-Baron G, Christ B, Marme D, Wilting J. Active interaction of human A375 melanoma cells with the lymphatics in vivo. Histochem Cell Biol. 2000; 114:373-85.

    PubMed  Google Scholar 

  270. Papoutsi M, Sleeman JP, Wilting J. Interaction of rat tumor cells with blood vessels and lymphatics of the avian chorioallantoic membrane. Microsc Res Tech. 2001; 55:100-7.

    PubMed  Google Scholar 

  271. Schoppmann SF, Birner P, Studer P, Breiteneder-Geleff S. Lymphatic microvessel density and lymphovascular invasion assessed by anti-podoplanin immunostaining in human breast cancer. Anticancer Res. 2001; 21:2351-5.

    PubMed  Google Scholar 

  272. Beasley NJ, Prevo R, Banerji S, Leek RD, Moore J, van Trappen P, Cox G, Harris AL, Jackson DG. Intratumoral lymphangiogenesis and lymph node metastasis in head and neck cancer. Cancer Res. 2002; 62:1315-20.

    PubMed  Google Scholar 

  273. Jain RK, Fenton BT. Intratumoral lymphatic vessels: a case of mistaken identity or malfunction? J Natl Cancer Inst. 2002; 94:417-21.

    PubMed  Google Scholar 

  274. Kurebayashi J, Otsuki T, Kunisue H, Mikami Y, Tanaka K, Yamamoto S, Sonoo H. Expression of vascular endothelial growth factor (VEGF) family members in breast cancer. Jpn J Cancer Res. 1999; 90:977-81.

    PubMed  Google Scholar 

  275. Salven P, Lymboussaki A, Heikkila P, Jaaskela-Saari H, Enholm B, Aase K, von Euler G, Eriksson U, Alitalo K, Joensuu H. Vascular endothelial growth factors VEGF-B and VEGF-C are expressed in human tumors. Am J Pathol. 1998; 153:103-8.

    PubMed  Google Scholar 

  276. Akagi K, Ikeda Y, Miyazaki M, Abe T, Kinoshita J, Maehara Y, Sugimachi K. Vascular endothelial growth factor-C (VEGF-C) expression in human colorectal cancer tissues. Br J Cancer. 2000; 83:887-91.

    PubMed  Google Scholar 

  277. Andre T, Kotelevets L, Vaillant JC, Coudray AM, Weber L, Prevot S, Parc R, Gespach C, Chastre E. Vegf, Vegf-B, Vegf-C and their receptors KDR, FLT-1 and FLT-4 during the neoplastic progression of human colonic mucosa. Int J Cancer. 2000; 86:174-81.

    PubMed  Google Scholar 

  278. Niki T, Iba S, Tokunou M, Yamada T, Matsuno Y, Hirohashi S. Expression of vascular endothelial growth factors A, B, C, and D and their relationships to lymph node status in lung adenocarcinoma. Clin Cancer Res. 2000; 6:2431-9.

    PubMed  Google Scholar 

  279. Ohta Y, Nozawa H, Tanaka Y, Oda M, Watanabe Y. Increased vascular endothelial growth factor and vascular endothelial growth factor-c and decreased nm23 expression associated with microdissemination in the lymph nodes in stage I non-small cell lung cancer. J Thorac Cardiovasc Surg. 2000; 119:804-13.

    PubMed  Google Scholar 

  280. Bunone G, Vigneri P, Mariani L, Buto S, Collini P, Pilotti S, Pierotti MA, Bongarzone I. Expression of angiogenesis stimulators and inhibitors in human thyroid tumors and correlation with clinical pathological features. Am J Pathol. 1999; 155:1967-76.

    PubMed  Google Scholar 

  281. Ohta Y, Shridhar V, Bright RK, Kalemkerian GP, Du W, Carbone M, Watanabe Y, Pass HI. VEGF and VEGF type C play an important role in angiogenesis and lymphangiogenesis in human malignant mesothelioma tumours. Br J Cancer. 1999; 81:54-61.

    PubMed  Google Scholar 

  282. Fellmer PT, Sato K, Tanaka R, Okamoto T, Kato Y, Kobayashi M, Shibuya M, Obara T. Vascular endothelial growth factor-C gene expression in papillary and follicular thyroid carcinomas. Surgery. 1999; 126:1056-61; discussion 1061-2.

    PubMed  Google Scholar 

  283. Shushanov S, Bronstein M, Adelaide J, Jussila L, Tchipysheva T, Jacquemier J, Stavrovskaya A, Birnbaum D, Karamysheva A. VEGFc and VEGFR3 expression in human thyroid pathologies. Int J Cancer. 2000; 86:47-52.

    PubMed  Google Scholar 

  284. Yonemura Y, Endo Y, Fujita H, Fushida S, Ninomiya I, Bandou E, Taniguchi K, Miwa K, Ohoyama S, Sugiyama K, Sasaki T. Role of vascular endothelial growth factor C expression in the development of lymph node metastasis in gastric cancer. Clin Cancer Res. 1999; 5:1823-9.

    PubMed  Google Scholar 

  285. Eggert A, Ikegaki N, Kwiatkowski J, Zhao H, Brodeur GM, Himelstein BP. High-level expression of angiogenic factors is associated with advanced tumor stage in human neuroblastomas. Clin Cancer Res. 2000; 6:1900-8.

    PubMed  Google Scholar 

  286. Tsurusaki T, Kanda S, Sakai H, Kanetake H, Saito Y, Alitalo K, Koji T. Vascular endothelial growth factor-C expression in human prostatic carcinoma and its relationship to lymph node metastasis. Br J Cancer. 1999; 80:309-13.

    PubMed  Google Scholar 

  287. Kubo H, Fujiwara T, Jussila L, Hashi H, Ogawa M, Shimizu K, Awane M, Sakai Y, Takabayashi A, Alitalo K, Yamaoka Y, Nishikawa SI. Involvement of vascular endothelial growth factor receptor-3 in maintenance of integrity of endothelial cell lining during tumor angiogenesis. Blood. 2000; 96:546-53.

    PubMed  Google Scholar 

  288. Dadras SS, Paul T, Bertoncini J, Brown LF, Muzikansky A, Jackson DG, Ellwanger U, Garbe C, Mihm MC, Detmar M. Tumor lymphangiogenesis: a novel prognostic indicator for cutaneous melanoma metastasis and survival. Am J Pathol. 2003; 162:1951-60.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2006 Springer

About this chapter

Cite this chapter

Shin, W., Rockson, S. (2006). Lymphangiogenesis: Recapitulation of Angiogensis in Health and Disease. In: Forough, R. (eds) New Frontiers in Angiogenesis. Springer, Dordrecht. https://doi.org/10.1007/1-4020-4327-9_8

Download citation

Publish with us

Policies and ethics