Emerging role of Sphingosine-1-phosphate in Inflammation, cancer, and lymphangiogenesis

Biomolecules

Volumn 3, Issue 3, 2013, Pages 408-434

  Huang, Wei Ching ^a   Nagahashi, Masayuki ^a   Terracina, Krista P ^a   Takabe, Kazuaki ^a  

^a VIRGINIA COMMONWEALTH UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Angiopoietin; Cancer; Inflammation; Lymphangiogenesis; Lymphatic endothelial cell; Metastasis; Sphingolipids; Sphingosine 1 phosphate; Spinster 2; VEGF

Indexed keywords

ABC 294640; ANGIOPOIETIN 1; ANGIOPOIETIN 2; ANGIOPOIETIN RECEPTOR; ANTINEOPLASTIC AGENT; FIBROBLAST GROWTH FACTOR 2; FINGOLIMOD; HISTONE DEACETYLASE; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERLEUKIN 6; NEUROPILIN 2; RAS PROTEIN; SPHINGOSINE 1 PHOSPHATE; SPHINGOSINE 1 PHOSPHATE RECEPTOR; STAT3 PROTEIN; TRANSCRIPTION FACTOR SOX18; UNCLASSIFIED DRUG; VASCULOTROPIN A; VASCULOTROPIN C; VASCULOTROPIN D; VASCULOTROPIN RECEPTOR 1; VASCULOTROPIN RECEPTOR 2; VASCULOTROPIN RECEPTOR 3;

ANGIOGENESIS; BINDING AFFINITY; BONE MARROW CELL; CANCER GROWTH; CELL MIGRATION; CELL PROLIFERATION; IMMUNE RESPONSE; INFLAMMATION; LYMPHANGIOGENESIS; LYMPHATIC SYSTEM; MULTIPLE SCLEROSIS; NEOPLASM; NONHUMAN; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; REVIEW;

EID: 84914155219     PISSN: None     EISSN: 2218273X     Source Type: Journal    
DOI: 10.3390/biom3030408     Document Type: Review

References (207)

1. Swartz, M.A. The physiology of the lymphatic system. Adv. Drug Deliv. Rev. 2001, 50, 3-20.
2. Rovenska, E.; Rovensky, J. Lymphatic vessels: Structure and function. Israel Med. Assoc. J. IMAJ 2011, 13, 762-768.
3. Schulte-Merker, S.; Sabine, A.; Petrova, T.V. Lymphatic vascular morphogenesis in development, physiology, and disease. J. Cell. Biol. 2011, 193, 607-618.
4. Baluk, P.; Fuxe, J.; Hashizume, H.; Romano, T.; Lashnits, E.; Butz, S.; Vestweber, D.; Corada, M.; Molendini, C.; Dejana, E.; et al. Functionally specialized junctions between endothelial cells of lymphatic vessels. J. Exp. Med. 2007, 204, 2349-2362.
5. Randolph, G.J.; Angeli, V.; Swartz, M.A. Dendritic-cell trafficking to lymph nodes through lymphatic vessels. Nat. Rev. Immunol. 2005, 5, 617-628.
6. Alitalo, K.; Tammela, T.; Petrova, T.V. Lymphangiogenesis in development and human disease. Nature 2005, 438, 946-953.
7. Tammela, T.; Alitalo, K. Lymphangiogenesis: Molecular mechanisms and future promise. Cell 2010, 140, 460-476.
8. Baluk, P.; Tammela, T.; Ator, E.; Lyubynska, N.; Achen, M.G.; Hicklin, D.J.; Jeltsch, M.; Petrova, T.V.; Pytowski, B.; Stacker, S.A.; et al. Pathogenesis of persistent lymphatic vessel hyperplasia in chronic airway inflammation. J. Clin. Invest. 2005, 115, 247-257.
9. Kunstfeld, R.; Hirakawa, S.; Hong, Y.K.; Schacht, V.; Lange-Asschenfeldt, B.; Velasco, P.; Lin, C.; Fiebiger, E.; Wei, X.; Wu, Y.; et al. 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, 1048-1057.
10. Kajiya, K.; Detmar, M. An important role of lymphatic vessels in the control of UVB-induced edema formation and inflammation. J. Invest. Dermatol. 2006, 126, 919-921.
11. Zhang, Q.; Lu, Y.; Proulx, S.T.; Guo, R.; Yao, Z.; Schwarz, E.M.; Boyce, B.F.; Xing, L. Increased lymphangiogenesis in joints of mice with inflammatory arthritis. Arthritis Res. Ther. 2007, 9, R118.
12. Shibuya, M. Vascular endothelial growth factor and its receptor system: Physiological functions in angiogenesis and pathological roles in various diseases. J. Biochem. 2013, 153, 13-19.
13. Lohela, M.; Bry, M.; Tammela, T.; Alitalo, K. VEGFs and receptors involved in angiogenesis versus lymphangiogenesis. Curr. Opin. Cell Biol. 2009, 21, 154-165.
14. Olsson, A.K.; Dimberg, A.; Kreuger, J.; Claesson-Welsh, L. VEGF receptor signalling-in control of vascular function. Nat. Rev. Mol. Cell. Biol. 2006, 7, 359-371.
15. Pepper, M.S.; Skobe, M. Lymphatic endothelium: Morphological, molecular and functional properties. J. Cell. Biol. 2003, 163, 209-213.
16. Karpanen, T.; Alitalo, K. Molecular biology and pathology of lymphangiogenesis. Annu. Rev. Pathol. 2008, 3, 367-397.
17. Alitalo, K. Growth factors controlling angiogenesis and lymphangiogenesis. Ugeskrift Laeger 2002, 164, 3170-3172.
18. Kaipainen, A.; Korhonen, J.; Mustonen, T.; van Hinsbergh, V.W.; Fang, G.H.; 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. USA 1995, 92, 3566-3570.
19. Saaristo, A.; Karkkainen, M.J.; Alitalo, K. Insights into the molecular pathogenesis and targeted treatment of lymphedema. Ann. N.Y. Acad. Sci. 2002, 979, 94-110.
20. Makinen, T.; Jussila, L.; Veikkola, T.; Karpanen, T.; Kettunen, M.I.; Pulkkanen, K.J.; Kauppinen, R.; Jackson, D.G.; Kubo, H.; Nishikawa, S.; et al. Inhibition of lymphangiogenesis with resulting lymphedema in transgenic mice expressing soluble VEGF receptor-3. Nat. Med. 2001, 7, 199-205.
21. 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, 290-298.
22. Tammela, T.; Saaristo, A.; Holopainen, T.; Lyytikka, J.; Kotronen, A.; Pitkonen, M.; Abo-Ramadan, U.; Yla-Herttuala, S.; Petrova, T.V.; Alitalo, K. Therapeutic differentiation and maturation of lymphatic vessels after lymph node dissection and transplantation. Nat. Med. 2007, 13, 1458-1466.
23. Karkkainen, M.J.; Saaristo, A.; Jussila, L.; Karila, K.A.; Lawrence, E.C.; Pajusola, K.; Bueler, H.; Eichmann, A.; Kauppinen, R.; Kettunen, M.I.; et al. A model for gene therapy of human hereditary lymphedema. Proc. Natl. Acad. Sci. USA 2001, 98, 12677-12682.
24. Saaristo, A.; Veikkola, T.; Tammela, T.; Enholm, B.; Karkkainen, M.J.; Pajusola, K.; Bueler, H.; Yla-Herttuala, S.; Alitalo, K. Lymphangiogenic gene therapy with minimal blood vascular side effects. J. Exp. Med. 2002, 196, 719-730.
25. Karkkainen, M.J.; Haiko, P.; Sainio, K.; Partanen, J.; Taipale, J.; Petrova, T.V.; Jeltsch, M.; Jackson, D.G.; Talikka, M.; Rauvala, H.; et al. Vascular endothelial growth factor C is required for sprouting of the first lymphatic vessels from embryonic veins. Nat. Immunol. 2004, 5, 74-80.
26. Veikkola, T.; Jussila, L.; Makinen, T.; Karpanen, T.; Jeltsch, M.; Petrova, T.V.; Kubo, H.; Thurston, G.; McDonald, D.M.; Achen, M.G.; et al. Signalling via vascular endothelial growth factor receptor-3 is sufficient for lymphangiogenesis in transgenic mice. EMBO J. 2001, 20, 1223-1231.
27. Haiko, P.; Makinen, T.; Keskitalo, S.; Taipale, J.; Karkkainen, M.J.; Baldwin, M.E.; Stacker, S.A.; Achen, M.G.; Alitalo, K. Deletion of vascular endothelial growth factor C (VEGF-C) and VEGF-D is not equivalent to VEGF receptor 3 deletion in mouse embryos. Mol. Cell. Biol. 2008, 28, 4843-4850.
28. Baldwin, M.E.; Halford, M.M.; Roufail, S.; Williams, R.A.; Hibbs, M.L.; Grail, D.; Kubo, H.; Stacker, S.A.; Achen, M.G. Vascular endothelial growth factor D is dispensable for development of the lymphatic system. Mol. Cell. Biol.2005, 25, 2441-2449.
29. 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, 3829-3837.
30. Partanen, T.A.; Arola, J.; Saaristo, A.; Jussila, L.; Ora, A.; Miettinen, M.; Stacker, S.A.; Achen, M.G.; 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, 2087-2096.
31. Lymboussaki, A.; Olofsson, B.; Eriksson, U.; Alitalo, K. Vascular endothelial growth factor (VEGF) and VEGF-C show overlapping binding sites in embryonic endothelia and distinct sites in differentiated adult endothelia. Circ. Res. 1999, 85, 992-999.
32. Achen, M.G.; Jeltsch, M.; Kukk, E.; Makinen, T.; Vitali, A.; Wilks, A.F.; Alitalo, K.; Stacker, S.A. 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. USA 1998, 95, 548-553.
33. 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, 3898-3911.
34. Stacker, S.A.; Stenvers, K.; Caesar, C.; Vitali, A.; Domagala, T.; Nice, E.; Roufail, S.; Simpson, R.J.; Moritz, R.; Karpanen, T.; et al. Biosynthesis of vascular endothelial growth factor-D involves proteolytic processing which generates non-covalent homodimers. J. Biol. Chem. 1999, 274, 32127-32136.
35. Eichmann, A.; Makinen, T.; Alitalo, K. Neural guidance molecules regulate vascular remodeling and vessel navigation. Genes Dev. 2005, 19, 1013-1021.
36. Karpanen, T.; Heckman, C.A.; Keskitalo, S.; Jeltsch, M.; Ollila, H.; Neufeld, G.; Tamagnone, L.; Alitalo, K. Functional interaction of VEGF-C and VEGF-D with neuropilin receptors. FASEB J. 2006, 20, 1462-1472.
37. Caunt, M.; Mak, J.; Liang, W.C.; Stawicki, S.; Pan, Q.; Tong, R.K.; Kowalski, J.; Ho, C.; Reslan, H.B.; Ross, J.; et al. Blocking neuropilin-2 function inhibits tumor cell metastasis. Cancer Cell 2008, 13, 331-342.
38. Yuan, L.; Moyon, D.; Pardanaud, L.; Breant, C.; Karkkainen, M.J.; Alitalo, K.; Eichmann, A. Abnormal lymphatic vessel development in neuropilin 2 mutant mice. Development 2002, 129, 4797-4806.
39. Hirakawa, S.; Kodama, S.; Kunstfeld, R.; Kajiya, K.; Brown, L.F.; Detmar, M. VEGF-A induces tumor and sentinel lymph node lymphangiogenesis and promotes lymphatic metastasis. J. Exp. Med. 2005, 201, 1089-1099.
40. Halin, C.; Tobler, N.E.; Vigl, B.; Brown, L.F.; Detmar, M. VEGF-A produced by chronically inflamed tissue induces lymphangiogenesis in draining lymph nodes. Blood 2007, 110, 3158-3167.
41. Nagy, J.A.; Vasile, E.; Feng, D.; Sundberg, C.; Brown, L.F.; Detmar, M.J.; Lawitts, J.A.; Benjamin, L.; Tan, X.; Manseau, E.J.; et al. Vascular permeability factor/vascular endothelial growth factor induces lymphangiogenesis as well as angiogenesis. J. Exp. Med. 2002, 196, 1497-1506.
42. Augustin, H.G.; Koh, G.Y.; Thurston, G.; Alitalo, K. Control of vascular morphogenesis and homeostasis through the angiopoietin-Tie system. Nat. Rev. Mol. Cell. Biol. 2009, 10, 165-177.
43. Ward, N.L.; Dumont, D.J. The angiopoietins and Tie2/Tek: Adding to the complexity of cardiovascular development. Semin. Cell Dev. Biol. 2002, 13, 19-27.
44. Yancopoulos, G.D.; Davis, S.; Gale, N.W.; Rudge, J.S.; Wiegand, S.J.; Holash, J. Vascular-specific growth factors and blood vessel formation. Nature 2000, 407, 242-248.
45. Puri, M.C.; 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, 5884-5891.
46. Dumont, D.J.; Gradwohl, G.; Fong, G.H.; Puri, M.C.; Gertsenstein, M.; Auerbach, A.; Breitman, M.L. 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, 1897-1909.
47. Sato, T.N.; 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, 70-74.
48. Morisada, T.; Oike, Y.; Yamada, Y.; Urano, T.; Akao, M.; Kubota, Y.; Maekawa, H.; Kimura, Y.; Ohmura, M.; Miyamoto, T.; et al. Angiopoietin-1 promotes LYVE-1-positive lymphatic vessel formation. Blood 2005, 105, 4649-4656.
49. Tammela, T.; Saaristo, A.; Lohela, M.; Morisada, T.; Tornberg, J.; Norrmen, C.; Oike, Y.; Pajusola, K.; Thurston, G.; Suda, T.; et al. Angiopoietin-1 promotes lymphatic sprouting and hyperplasia. Blood 2005, 105, 4642-4648.
50. Kim, K.E.; Cho, C.H.; Kim, H.Z.; Baluk, P.; McDonald, D.M.; Koh, G.Y. In vivo actions of angiopoietins on quiescent and remodeling blood and lymphatic vessels in mouse airways and skin. Arterioscler. Thromb. Vasc. Biol. 2007, 27, 564-570.
51. Davis, S.; Aldrich, T.H.; Jones, P.F.; Acheson, A.; Compton, D.L.; Jain, V.; Ryan, T.E.; Bruno, J.; Radziejewski, C.; Maisonpierre, P.C.; et al. Isolation of angiopoietin-1, a ligand for the TIE2 receptor, by secretion-trap expression cloning. Cell 1996, 87, 1161-1169.
52. Maisonpierre, P.C.; Suri, C.; Jones, P.F.; Bartunkova, S.; Wiegand, S.J.; Radziejewski, C.; Compton, D.; McClain, J.; Aldrich, T.H.; Papadopoulos, N.; et al. Angiopoietin-2, a natural antagonist for Tie2 that disrupts in vivo angiogenesis. Science 1997, 277, 55-60.
53. Valenzuela, D.M.; Griffiths, J.A.; Rojas, J.; Aldrich, T.H.; Jones, P.F.; Zhou, H.; McClain, J.; Copeland, N.G.; Gilbert, D.J.; Jenkins, N.A.; et al. Angiopoietins 3 and 4: Diverging gene counterparts in mice and humans. Proc. Natl. Acad. Sci. USA 1999, 96, 1904-1909.
54. Gale, N.W.; Thurston, G.; Hackett, S.F.; Renard, R.; Wang, Q.; McClain, J.; Martin, C.; Witte, C.; Witte, M.H.; Jackson, D.; et al. Angiopoietin-2 is required for postnatal angiogenesis and lymphatic patterning, and only the latter role is rescued by Angiopoietin-1. Dev. Cell 2002, 3, 411-423.
55. Hong, Y.K.; Harvey, N.; Noh, Y.H.; Schacht, V.; Hirakawa, S.; Detmar, M.; Oliver, G. Prox1 is a master control gene in the program specifying lymphatic endothelial cell fate. Dev. Dyn. 2002, 225, 351-357.
56. Petrova, T.V.; Makinen, T.; Makela, T.P.; Saarela, J.; Virtanen, I.; Ferrell, R.E.; Finegold, D.N.; Kerjaschki, D.; Yla-Herttuala, S.; Alitalo, K. Lymphatic endothelial reprogramming of vascular endothelial cells by the Prox-1 homeobox transcription factor. EMBO J. 2002, 21, 4593-4599.
57. Veikkola, T.; Alitalo, K. Dual role of Ang2 in postnatal angiogenesis and lymphangiogenesis. Dev. Cell 2002, 3, 302-304.
58. Zumsteg, A.; Christofori, G. Myeloid cells and lymphangiogenesis. Cold Spring Harb. Persp. Med. 2012, 2, a006494.
59. Aurora, A.B.; Baluk, P.; Zhang, D.; Sidhu, S.S.; Dolganov, G.M.; Basbaum, C.; McDonald, D.M.; Killeen, N. Immune complex-dependent remodeling of the airway vasculature in response to a chronic bacterial infection. J. Immunol. 2005, 175, 6319-6326.
60. Angeli, V.; Ginhoux, F.; Llodra, J.; Quemeneur, L.; Frenette, P.S.; Skobe, M.; Jessberger, R.; Merad, M.; Randolph, G.J. B cell-driven lymphangiogenesis in inflamed lymph nodes enhances dendritic cell mobilization. Immunity 2006, 24, 203-215.
61. Kang, S.; Lee, S.P.; Kim, K.E.; Kim, H.Z.; Memet, S.; Koh, G.Y. Toll-like receptor 4 in lymphatic endothelial cells contributes to LPS-induced lymphangiogenesis by chemotactic recruitment of macrophages. Blood 2009, 113, 2605-2613.
62. Flister, M.J.; Wilber, A.; Hall, K.L.; Iwata, C.; Miyazono, K.; Nisato, R.E.; Pepper, M.S.; Zawieja, D.C.; Ran, S. Inflammation induces lymphangiogenesis through up-regulation of VEGFR-3 mediated by NF-kappaB and Prox1. Blood 2010, 115, 418-429.
63. Machnik, A.; Neuhofer, W.; Jantsch, J.; Dahlmann, A.; Tammela, T.; Machura, K.; Park, J.K.; Beck, F.X.; Muller, D.N.; Derer, W.; et al. Macrophages regulate salt-dependent volume and blood pressure by a vascular endothelial growth factor-C-dependent buffering mechanism. Nat. Med. 2009, 15, 545-552.
64. Kubota, Y.; Takubo, K.; Shimizu, T.; Ohno, H.; Kishi, K.; Shibuya, M.; Saya, H.; Suda, T. M-CSF inhibition selectively targets pathological angiogenesis and lymphangiogenesis. J. Exp. Med. 2009, 206, 1089-1102.
65. Schoppmann, S.F.; Birner, P.; Stockl, J.; Kalt, R.; Ullrich, R.; Caucig, C.; Kriehuber, E.; Nagy, K.; Alitalo, K.; Kerjaschki, D. Tumor-associated macrophages express lymphatic endothelial growth factors and are related to peritumoral lymphangiogenesis. Am. J. Pathol. 2002, 161, 947-956.
66. Jeon, B.H.; Jang, C.; Han, J.; Kataru, R.P.; Piao, L.; Jung, K.; Cha, H.J.; Schwendener, R.A.; Jang, K.Y.; Kim, K.S.; et al. Profound but dysfunctional lymphangiogenesis via vascular endothelial growth factor ligands from CD11b+ macrophages in advanced ovarian cancer. Cancer Res. 2008, 68, 1100-1109.
67. Zhang, B.; Wang, J.; Gao, J.; Guo, Y.; Chen, X.; Wang, B.; Rao, Z.; Chen, Z. Alternatively activated RAW264.7 macrophages enhance tumor lymphangiogenesis in mouse lung adenocarcinoma. J. Cell. Biochem. 2009, 107, 134-143.
68. Yang, H.; Kim, C.; Kim, M.J.; Schwendener, R.A.; Alitalo, K.; Heston, W.; Kim, I.; Kim, W.J.; Koh, G.Y. Soluble vascular endothelial growth factor receptor-3 suppresses lymphangiogenesis and lymphatic metastasis in bladder cancer. Mol. Cancer 2011, 10, 36.
69. Schoppmann, S.F.; Fenzl, A.; Nagy, K.; Unger, S.; Bayer, G.; Geleff, S.; Gnant, M.; Horvat, R.; Jakesz, R.; Birner, P. VEGF-C expressing tumor-associated macrophages in lymph node positive breast cancer: Impact on lymphangiogenesis and survival. Surgery 2006, 139, 839-846.
70. Moussai, D.; Mitsui, H.; Pettersen, J.S.; Pierson, K.C.; Shah, K.R.; Suarez-Farinas, M.; Cardinale, I.R.; Bluth, M.J.; Krueger, J.G.; Carucci, J.A. The human cutaneous squamous cell carcinoma microenvironment is characterized by increased lymphatic density and enhanced expression of macrophage-derived VEGF-C. J. Invest. Dermatol. 2011, 131, 229-236.
71. Algars, A.; Irjala, H.; Vaittinen, S.; Huhtinen, H.; Sundstrom, J.; Salmi, M.; Ristamaki, R.; Jalkanen, S. Type and location of tumor-infiltrating macrophages and lymphatic vessels predict survival of colorectal cancer patients. Int. J. Cancer J. Int. du Cancer 2012, 131, 864-873.
72. Wigle, J.T.; Harvey, N.; Detmar, M.; Lagutina, I.; Grosveld, G.; Gunn, M.D.; Jackson, D.G.; Oliver, G. An essential role for Prox1 in the induction of the lymphatic endothelial cell phenotype. EMBO J. 2002, 21, 1505-1513.
73. Yang, Y.; Garcia-Verdugo, J.M.; Soriano-Navarro, M.; Srinivasan, R.S.; Scallan, J.P.; Singh, M.K.; Epstein, J.A.; Oliver, G. Lymphatic endothelial progenitors bud from the cardinal vein and intersomitic vessels in mammalian embryos. Blood 2012, 120, 2340-2348.
74. Hagerling, R.; Pollmann, C.; Andreas, M.; Schmidt, C.; Nurmi, H.; Adams, R.H.; Alitalo, K.; Andresen, V.; Schulte-Merker, S.; Kiefer, F. A novel multistep mechanism for initial lymphangiogenesis in mouse embryos based on ultramicroscopy. EMBO J. 2013, 32, 629-644.
75. Mouta, C.; Heroult, M. Inflammatory triggers of lymphangiogenesis. Lymphat. Res. Biol. 2003, 1, 201-218.
76. Saharinen, P.; Tammela, T.; Karkkainen, M.J.; Alitalo, K. Lymphatic vasculature: Development, molecular regulation and role in tumor metastasis and inflammation. Trends Immunol. 2004, 25, 387-395.
77. Jackson, D.G. New molecular markers for the study of tumour lymphangiogenesis. Anticancer Res. 2001, 21, 4279-4283.
78. Sleeman, J.P.; Krishnan, J.; Kirkin, V.; Baumann, P. Markers for the lymphatic endothelium: In search of the holy grail? Microsc. Res. Tech. 2001, 55, 61-69.
79. Johnson, N.C.; Dillard, M.E.; Baluk, P.; McDonald, D.M.; Harvey, N.L.; Frase, S.L.; Oliver, G. Lymphatic endothelial cell identity is reversible and its maintenance requires Prox1 activity. Genes Dev. 2008, 22, 3282-3291.
80. Francois, M.; Caprini, A.; Hosking, B.; Orsenigo, F.; Wilhelm, D.; Browne, C.; Paavonen, K.; Karnezis, T.; Shayan, R.; Downes, M.; et al. Sox18 induces development of the lymphatic vasculature in mice. Nature 2008, 456, 643-647.
81. Lee, S.; Kang, J.; Yoo, J.; Ganesan, S.K.; Cook, S.C.; Aguilar, B.; Ramu, S.; Lee, J.; Hong, Y.K. Prox1 physically and functionally interacts with COUP-TFII to specify lymphatic endothelial cell fate. Blood 2009, 113, 1856-1859.
82. Srinivasan, R.S.; Geng, X.; Yang, Y.; Wang, Y.; Mukatira, S.; Studer, M.; Porto, M.P.; Lagutin, O.; Oliver, G. The nuclear hormone receptor Coup-TFII is required for the initiation and early maintenance of Prox1 expression in lymphatic endothelial cells. Genes Dev. 2010, 24, 696-707.
83. Yamazaki, T.; Yoshimatsu, Y.; Morishita, Y.; Miyazono, K.; Watabe, T. COUP-TFII regulates the functions of Prox1 in lymphatic endothelial cells through direct interaction. Genes Cells 2009, 14, 425-434.
84. Halin, C.; Detmar, M. An unexpected connection: Lymph node lymphangiogenesis and dendritic cell migration. Immunity 2006, 24, 129-131.
85. Angeli, V.; Randolph, G.J. Inflammation, lymphatic function, and dendritic cell migration. Lymphat. Res. Biol. 2006, 4, 217-228.
86. Chen, L.; Hamrah, P.; Cursiefen, C.; Zhang, Q.; Pytowski, B.; Streilein, J.W.; Dana, M.R. Vascular endothelial growth factor receptor-3 mediates induction of corneal alloimmunity. Nat. Med. 2004, 10, 813-815.
87. Greco, K.V.; Lara, P.F.; Oliveira-Filho, R.M.; Greco, R.V.; Sudo-Hayashi, L.S. Lymphatic regeneration across an incisional wound: Inhibition by dexamethasone and aspirin, and acceleration by a micronized purified flavonoid fraction. Eur. J. Pharmacol. 2006, 551, 131-142.
88. 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, 1499-1504
89. Kallskog, O.; Kampf, C.; Andersson, A.; Carlsson, P.O.; Hansell, P.; Johansson, M.; Jansson, L. Lymphatic vessels in pancreatic islets implanted under the renal capsule of rats. Am. J. Transplant. 2006, 6, 680-686.
90. Kerjaschki, D.; Huttary, N.; Raab, I.; Regele, H.; Bojarski-Nagy, K.; Bartel, G.; Krober, S.M.; Greinix, H.; Rosenmaier, A.; Karlhofer, F.; et al. Lymphatic endothelial progenitor cells contribute to de novo lymphangiogenesis in human renal transplants. Nat. Med. 2006, 12, 230-234.
91. Ling, S.; Qi, C.; Li, W.; Xu, J.; Kuang, W. The expression of vascular endothelial growth factor C in transplanted corneas. Curr. Eye Res. 2009, 34, 553-561.
92. Alitalo, A.; Detmar, M. Interaction of tumor cells and lymphatic vessels in cancer progression. Oncogene 2012, 31, 4499-4508.
93. Shields, J.D. Lymphatics: At the interface of immunity, tolerance, and tumor metastasis. Microcirculation 2011, 18, 517-531.
94. Zgraggen, S.; Ochsenbein, A.M.; Detmar, M. An important role of blood and lymphatic vessels in inflammation and allergy. J. Allergy (Cairo) 2013, 2013, 672381.
95. Sundar, S.S.; Ganesan, T.S. Role of lymphangiogenesis in cancer. J. Clin. Oncol. Off. J. Am. Soc. Clin. Oncol. 2007, 25, 4298-4307.
96. El-Chemaly, S.; Levine, S.J.; Moss, J. Lymphatics in lung disease. Ann. NY Acad. Sci. 2008, 1131, 195-202.
97. Oliver, G.; Alitalo, K. The lymphatic vasculature: Recent progress and paradigms. Annu. Rev. Cell Dev. Biol. 2005, 21, 457-483.
98. Baluk, P.; Yao, L.C.; Feng, J.; Romano, T.; Jung, S.S.; Schreiter, J.L.; Yan, L.; Shealy, D.J.; McDonald, D.M. TNF-alpha drives remodeling of blood vessels and lymphatics in sustained airway inflammation in mice. J. Clin. Invest. 2009, 119, 2954-2964.
99. Hoshida, T.; Isaka, N.; Hagendoorn, J.; di Tomaso, E.; Chen, Y.L.; Pytowski, B.; Fukumura, D.; Padera, T.P.; Jain, R.K. Imaging steps of lymphatic metastasis reveals that vascular endothelial growth factor-C increases metastasis by increasing delivery of cancer cells to lymph nodes: Therapeutic implications. Cancer Res. 2006, 66, 8065-8075.
100. Cursiefen, C.; Chen, L.; Borges, L.P.; Jackson, D.; Cao, J.; Radziejewski, C.; D'Amore, P.A.; Dana, M.R.; Wiegand, S.J.; Streilein, J.W. VEGF-A stimulates lymphangiogenesis and hemangiogenesis in inflammatory neovascularization via macrophage recruitment. J. Clin. Invest. 2004, 113, 1040-1050.
101. 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, 8413-8418.
102. Jeltsch, M.; Kaipainen, A.; Joukov, V.; Meng, X.; Lakso, M.; Rauvala, H.; Swartz, M.; Fukumura, D.; Jain, R.K.; Alitalo, K. Hyperplasia of lymphatic vessels in VEGF-C transgenic mice. Science 1997, 276, 1423-1425.
103. Guo, R.; Zhou, Q.; Proulx, S.T.; Wood, R.; Ji, R.C.; Ritchlin, C.T.; Pytowski, B.; Zhu, Z.; Wang, Y.J.; Schwarz, E.M.; et al. Inhibition of lymphangiogenesis and lymphatic drainage via vascular endothelial growth factor receptor 3 blockade increases the severity of inflammation in a mouse model of chronic inflammatory arthritis. Arthritis Rheumat. 2009, 60, 2666-2676.
104. Hamrah, P.; Chen, L.; Zhang, Q.; Dana, M.R. Novel expression of vascular endothelial growth factor receptor (VEGFR)-3 and VEGF-C on corneal dendritic cells. Am. J. Pathol. 2003, 163, 57-68.
105. Martinez-Corral, I.; Makinen, T. Regulation of lymphatic vascular morphogenesis: Implications for pathological (tumor) lymphangiogenesis. Exp. Cell. Res. 2013, 319, 1618-1625.
106. Nagahashi, M.; Ramachandran, S.; Rashid, O.M.; Takabe, K. Lymphangiogenesis: A new player in cancer progression. World J. Gastroenterol. WJG 2010, 16, 4003-4012.
107. Tammela, T.; He, Y.; Lyytikka, J.; Jeltsch, M.; Markkanen, J.; Pajusola, K.; Yla-Herttuala, S.; Alitalo, K. Distinct architecture of lymphatic vessels induced by chimeric vascular endothelial growth factor-C/vascular endothelial growth factor heparin-binding domain fusion proteins. Circ. Res. 2007, 100, 1468-1475.
108. He, Y.; Rajantie, I.; Pajusola, K.; Jeltsch, M.; Holopainen, T.; Yla-Herttuala, S.; Harding, T.; Jooss, K.; Takahashi, T.; Alitalo, K. Vascular endothelial cell growth factor receptor 3-mediated activation of lymphatic endothelium is crucial for tumor cell entry and spread via lymphatic vessels. Cancer Res. 2005, 65, 4739-4746.
109. Lin, F.J.; Chen, X.; Qin, J.; Hong, Y.K.; Tsai, M.J.; Tsai, S.Y. Direct transcriptional regulation of neuropilin-2 by COUP-TFII modulates multiple steps in murine lymphatic vessel development. J. Clin. Invest. 2010, 120, 1694-1707.
110. Duong, T.; Proulx, S.T.; Luciani, P.; Leroux, J.C.; Detmar, M.; Koopman, P.; Francois, M. Genetic ablation of SOX18 function suppresses tumor lymphangiogenesis and metastasis of melanoma in mice. Cancer Res. 2012, 72, 3105-3114.
111. Stacker, S.A.; Caesar, C.; Baldwin, M.E.; Thornton, G.E.; Williams, R.A.; Prevo, R.; Jackson, D.G.; Nishikawa, S.; Kubo, H.; Achen, M.G. VEGF-D promotes the metastatic spread of tumor cells via the lymphatics. Nat. Med. 2001, 7, 186-191.
112. Mandriota, S.J.; Jussila, L.; Jeltsch, M.; Compagni, A.; Baetens, D.; Prevo, R.; Banerji, S.; Huarte, J.; Montesano, R.; Jackson, D.G.; et al. Vascular endothelial growth factor-C-mediated lymphangiogenesis promotes tumour metastasis. EMBO J. 2001, 20, 672-682.
113. Karpanen, T.; Egeblad, M.; Karkkainen, M.J.; 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, 1786-1790.
114. Skobe, M.; Hawighorst, T.; Jackson, D.G.; 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, 192-198.
115. 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 receptor 3 signaling. J. Natl. Cancer Instit. 2002, 94, 819-825.
116. Krishnan, J.; Kirkin, V.; Steffen, A.; Hegen, M.; Weih, D.; Tomarev, S.; Wilting, J.; Sleeman, J.P. Differential in vivo and in vitro expression of vascular endothelial growth factor (VEGF)-C and VEGF-D in tumors and its relationship to lymphatic metastasis in immunocompetent rats. Cancer Res. 2003, 63, 713-722.
117. Kopfstein, L.; Veikkola, T.; Djonov, V.G.; Baeriswyl, V.; Schomber, T.; Strittmatter, K.; Stacker, S.A.; Achen, M.G.; Alitalo, K.; Christofori, G. Distinct roles of vascular endothelial growth factor-D in lymphangiogenesis and metastasis. Am. J. Pathol. 2007, 170, 1348-1361.
118. Hirakawa, S.; Brown, L.F.; Kodama, S.; Paavonen, K.; Alitalo, K.; Detmar, M. VEGF-C-induced lymphangiogenesis in sentinel lymph nodes promotes tumor metastasis to distant sites. Blood 2007, 109, 1010-1017.
119. Christiansen, A.; Detmar, M. Lymphangiogenesis and cancer. Genes Cancer 2011, 2, 1146-1158.
120. Cao, R.; Ji, H.; Feng, N.; Zhang, Y.; Yang, X.; Andersson, P.; Sun, Y.; Tritsaris, K.; Hansen, A.J.; Dissing, S.; et al. Collaborative interplay between FGF-2 and VEGF-C promotes lymphangiogenesis and metastasis. Proc. Natl. Acad. Sci. USA 2012, 109, 15894-15899.
121. Larrieu-Lahargue, F.; Welm, A.L.; Bouchecareilh, M.; Alitalo, K.; Li, D.Y.; Bikfalvi, A.; Auguste, P. Blocking fibroblast growth factor receptor signaling inhibits tumor growth, lymphangiogenesis, and metastasis. PLoS One 2012, 7, e39540.
122. O'Farrell, A.M.; Abrams, T.J.; Yuen, H.A.; Ngai, T.J.; Louie, S.G.; Yee, K.W.; Wong, L.M.; Hong, W.; Lee, L.B.; Town, A.; et al. SU11248 is a novel FLT3 tyrosine kinase inhibitor with potent activity in vitro and in vivo. Blood 2003, 101, 3597-3605.
123. Nasarre, P.; Thomas, M.; Kruse, K.; Helfrich, I.; Wolter, V.; Deppermann, C.; Schadendorf, D.; Thurston, G.; Fiedler, U.; Augustin, H.G. Host-derived angiopoietin-2 affects early stages of tumor development and vessel maturation but is dispensable for later stages of tumor growth. Cancer Res. 2009, 69, 1324-1333.
124. Lin, P.; Polverini, P.; Dewhirst, M.; Shan, S.; Rao, P.S.; Peters, K. Inhibition of tumor angiogenesis using a soluble receptor establishes a role for Tie2 in pathologic vascular growth. J. Clin. Invest. 1997, 100, 2072-2078.
125. Lin, P.; Buxton, J.A.; Acheson, A.; Radziejewski, C.; Maisonpierre, P.C.; Yancopoulos, G.D.; Channon, K.M.; Hale, L.P.; Dewhirst, M.W.; George, S.E.; et al. Antiangiogenic gene therapy targeting the endothelium-specific receptor tyrosine kinase Tie2. Proc. Natl. Acad. Sci. USA 1998, 95, 8829-8834.
126. He, Y.; Rajantie, I.; Ilmonen, M.; Makinen, T.; Karkkainen, M.J.; Haiko, P.; Salven, P.; Alitalo, K. Preexisting lymphatic endothelium but not endothelial progenitor cells are essential for tumor lymphangiogenesis and lymphatic metastasis. Cancer Res. 2004, 64, 3737-3740.
127. Gordon, E.J.; Rao, S.; Pollard, J.W.; Nutt, S.L.; Lang, R.A.; Harvey, N.L. Macrophages define dermal lymphatic vessel calibre during development by regulating lymphatic endothelial cell proliferation. Development 2010, 137, 3899-3910.
128. Maceyka, M.; Harikumar, K.B.; Milstien, S.; Spiegel, S. Sphingosine-1-phosphate signaling and its role in disease. Trends Cell Biol. 2012, 22, 50-60.
129. Takabe, K.; Paugh, S.W.; Milstien, S.; Spiegel, S. "Inside-out" signaling of sphingosine-1-phosphate: Therapeutic targets. Pharmacol. Rev. 2008, 60, 181-195.
130. Le Stunff, H.; Milstien, S.; Spiegel, S. Generation and metabolism of bioactive sphingosine-1-phosphate. J. Cell. Biochem. 2004, 92, 882-899.
131. Ghosh, T.K.; Bian, J.; Gill, D.L. Intracellular calcium release mediated by sphingosine derivatives generated in cells. Science 1990, 248, 1653-1656.
132. Ghosh, T.K.; Bian, J.; Gill, D.L. Sphingosine 1-phosphate generated in the endoplasmic reticulum membrane activates release of stored calcium. J. Biol. Chem. 1994, 269, 22628-22635.
133. Mattie, M.; Brooker, G.; Spiegel, S. Sphingosine-1-phosphate, a putative second messenger, mobilizes calcium from internal stores via an inositol trisphosphate-independent pathway. J. Biol. Chem. 1994, 269, 3181-3188.
134. Alvarez, S.E.; Harikumar, K.B.; Hait, N.C.; Allegood, J.; Strub, G.M.; Kim, E.Y.; Maceyka, M.; Jiang, H.; Luo, C.; Kordula, T.; et al. Sphingosine-1-phosphate is a missing cofactor for the E3 ubiquitin ligase TRAF2. Nature 2010, 465, 1084-1088.
135. Hait, N.C.; Allegood, J.; Maceyka, M.; Strub, G.M.; Harikumar, K.B.; Singh, S.K.; Luo, C.; Marmorstein, R.; Kordula, T.; Milstien, S.; et al. Regulation of histone acetylation in the nucleus by sphingosine-1-phosphate. Science 2009, 325, 1254-1257.
136. Sato, K.; Malchinkhuu, E.; Horiuchi, Y.; Mogi, C.; Tomura, H.; Tosaka, M.; Yoshimoto, Y.; Kuwabara, A.; Okajima, F. Critical role of ABCA1 transporter in sphingosine 1-phosphate release from astrocytes. J. Neurochem. 2007, 103, 2610-2619.
137. Mitra, P.; Oskeritzian, C.A.; Payne, S.G.; Beaven, M.A.; Milstien, S.; Spiegel, S. Role of ABCC1 in export of sphingosine-1-phosphate from mast cells. Proc. Natl. Acad. Sci. USA 2006, 103, 16394-16399.
138. Takabe, K.; Kim, R.H.; Allegood, J.C.; Mitra, P.; Ramachandran, S.; Nagahashi, M.; Harikumar, K.B.; Hait, N.C.; Milstien, S.; Spiegel, S. Estradiol induces export of sphingosine 1-phosphate from breast cancer cells via ABCC1 and ABCG2. J. Biol. Chem. 2010, 285, 10477-10486
139. Kawahara, A.; Nishi, T.; Hisano, Y.; Fukui, H.; Yamaguchi, A.; Mochizuki, N. The sphingolipid transporter spns2 functions in migration of zebrafish myocardial precursors. Science 2009, 323, 524-527.
140. Nagahashi, M.; Kim, E.Y.; Yamada, A.; Ramachandran, S.; Allegood, J.C.; Hait, N.C.; Maceyka, M.; Milstien, S.; Takabe, K.; Spiegel, S. Spns2, a transporter of phosphorylated sphingoid bases, regulates their blood and lymph levels, and the lymphatic network. FASEB J. 2013, 27, 1001-1011.
141. Pham, T.H.; Baluk, P.; Xu, Y.; Grigorova, I.; Bankovich, A.J.; Pappu, R.; Coughlin, S.R.; McDonald, D.M.; Schwab, S.R.; Cyster, J.G. Lymphatic endothelial cell sphingosine kinase activity is required for lymphocyte egress and lymphatic patterning. J. Exp. Med. 2010, 207, 17-27.
142. Kim, R.H.; Takabe, K.; Milstien, S.; Spiegel, S. Export and functions of sphingosine-1-phosphate. Biochim. Biophys. Acta 2009, 1791, 692-696.
143. Mendoza, A.; Breart, B.; Ramos-Perez, W.D.; Pitt, L.A.; Gobert, M.; Sunkara, M.; Lafaille, J.J.; Morris, A.J.; Schwab, S.R. The transporter Spns2 is required for secretion of lymph but not plasma sphingosine-1-phosphate. Cell. Rep. 2012, 2, 1104-1110.
144. Hisano, Y.; Kobayashi, N.; Kawahara, A.; Yamaguchi, A.; Nishi, T. The sphingosine 1-phosphate transporter, SPNS2, functions as a transporter of the phosphorylated form of the immunomodulating agent FTY720. J. Biol. Chem. 2011, 286, 1758-1766.
145. Fukuhara, S.; Simmons, S.; Kawamura, S.; Inoue, A.; Orba, Y.; Tokudome, T.; Sunden, Y.; Arai, Y.; Moriwaki, K.; Ishida, J.; et al. The sphingosine-1-phosphate transporter Spns2 expressed on endothelial cells regulates lymphocyte trafficking in mice. J. Clin. Invest. 2012, 122, 1416-1426.
146. Nijnik, A.; Clare, S.; Hale, C.; Chen, J.; Raisen, C.; Mottram, L.; Lucas, M.; Estabel, J.; Ryder, E.; Adissu, H.; et al. The role of sphingosine-1-phosphate transporter Spns2 in immune system function. J. Immunol. 2012, 189, 102-111.
147. Hisano, Y.; Kobayashi, N.; Yamaguchi, A.; Nishi, T. Mouse SPNS2 functions as a sphingosine-1-phosphate transporter in vascular endothelial cells. PLoS One 2012, 7, e38941.
148. Yamada, A.; Ishikawa, T.; Ota, I.; Kimura, M.; Shimizu, D.; Tanabe, M.; Chishima, T.; Sasaki, T.; Ichikawa, Y.; Morita, S.; et al. High expression of ATP-binding cassette transporter ABCC11 in breast tumors is associated with aggressive subtypes and low disease-free survival. Breast Cancer Res. Treat. 2013, 137, 773-782.
149. Rivera, J.; Proia, R.L.; Olivera, A. The alliance of sphingosine-1-phosphate and its receptors in immunity. Nat. Rev. Immunol. 2008, 8, 753-763.
150. Spiegel, S.; Milstien, S. The outs and the ins of sphingosine-1-phosphate in immunity. Nat. Rev. Immunol. 2011, 11, 403-415.
151. Pyne, N.J.; Pyne, S. Sphingosine 1-phosphate and cancer. Nat. Rev. Cancer 2010, 10, 489-503.
152. Chi, H. Sphingosine-1-phosphate and immune regulation: Trafficking and beyond. Trends Pharmacol. Sci. 2011, 32, 16-24.
153. Pham, T.H.; Okada, T.; Matloubian, M.; Lo, C.G.; Cyster, J.G. S1P1 receptor signaling overrides retention mediated by G alpha i-coupled receptors to promote T cell egress. Immunity 2008, 28, 122-133.
154. Cyster, J.G. B cell follicles and antigen encounters of the third kind. Nat. Immunol. 2010, 11, 989-996.
155. Jenne, C.N.; Enders, A.; Rivera, R.; Watson, S.R.; Bankovich, A.J.; Pereira, J.P.; Xu, Y.; Roots, C.M.; Beilke, J.N.; Banerjee, A.; et al. T-bet-dependent S1P5 expression in NK cells promotes egress from lymph nodes and bone marrow. J. Exp. Med. 2009, 206, 2469-2481.
156. Allende, M.L.; Bektas, M.; Lee, B.G.; Bonifacino, E.; Kang, J.; Tuymetova, G.; Chen, W.; Saba, J.D.; Proia, R.L. Sphingosine-1-phosphate lyase deficiency produces a pro-inflammatory response while impairing neutrophil trafficking. J. Biol. Chem. 2011, 286, 7348-7358.
157. Liu, Y.; Wada, R.; Yamashita, T.; Mi, Y.; Deng, C.X.; Hobson, J.P.; Rosenfeldt, H.M.; Nava, V.E.; Chae, S.S.; Lee, M.J.; et al. Edg-1, the G protein-coupled receptor for sphingosine-1-phosphate, is essential for vascular maturation. J. Clin. Invest. 2000, 106, 951-961.
158. Kono, M.; Mi, Y.; Liu, Y.; Sasaki, T.; Allende, M.L.; Wu, Y.P.; Yamashita, T.; Proia, R.L. The sphingosine-1-phosphate receptors S1P1, S1P2, and S1P3 function coordinately during embryonic angiogenesis. J. Biol. Chem. 2004, 279, 29367-29373.
159. Brinkmann, V.; Billich, A.; Baumruker, T.; Heining, P.; Schmouder, R.; Francis, G.; Aradhye, S.; Burtin, P. Fingolimod (FTY720): Discovery and development of an oral drug to treat multiple sclerosis. Nat. Rev. Drug Discov. 2010, 9, 883-897.
160. Allende, M.L.; Sasaki, T.; Kawai, H.; Olivera, A.; Mi, Y.; van Echten-Deckert, G.; Hajdu, R.; Rosenbach, M.; Keohane, C.A.; Mandala, S.; et al. Mice deficient in sphingosine kinase 1 are rendered lymphopenic by FTY720. J. Biol. Chem. 2004, 279, 52487-52492.
161. Kharel, Y.; Lee, S.; Snyder, A.H.; Sheasley-O'neill, S.L.; Morris, M.A.; Setiady, Y.; Zhu, R.; Zigler, M.A.; Burcin, T.L.; Ley, K.; et al. Sphingosine kinase 2 is required for modulation of lymphocyte traffic by FTY720. J. Biol. Chem. 2005, 280, 36865-36872.
162. Zemann, B.; Kinzel, B.; Muller, M.; Reuschel, R.; Mechtcheriakova, D.; Urtz, N.; Bornancin, F.; Baumruker, T.; Billich, A. Sphingosine kinase type 2 is essential for lymphopenia induced by the immunomodulatory drug FTY720. Blood 2006, 107, 1454-1458.
163. Matloubian, M.; Lo, C.G.; Cinamon, G.; Lesneski, M.J.; Xu, Y.; Brinkmann, V.; Allende, M.L.; Proia, R.L.; Cyster, J.G. Lymphocyte egress from thymus and peripheral lymphoid organs is dependent on S1P receptor 1. Nature 2004, 427, 355-360.
164. Graler, M.H.; Goetzl, E.J. The immunosuppressant FTY720 down-regulates sphingosine 1-phosphate G-protein-coupled receptors. FASEB J. 2004, 18, 551-553.
165. Cyster, J.G. Chemokines, sphingosine-1-phosphate, and cell migration in secondary lymphoid organs. Annu. Rev. Immunol. 2005, 23, 127-159.
166. Deguchi, Y.; Andoh, A.; Yagi, Y.; Bamba, S.; Inatomi, O.; Tsujikawa, T.; Fujiyama, Y. The S1P receptor modulator FTY720 prevents the development of experimental colitis in mice. Oncol. Rep. 2006, 16, 699-703.
167. Wang, F.; Tan, W.; Guo, D.; He, S. Reduction of CD4 positive T cells and improvement of pathological changes of collagen-induced arthritis by FTY720. Eur. J. Pharmacol. 2007, 573, 230-240.
168. Idzko, M.; Hammad, H.; van Nimwegen, M.; Kool, M.; Muller, T.; Soullie, T.; Willart, M.A.; Hijdra, D.; Hoogsteden, H.C.; Lambrecht, B.N. Local application of FTY720 to the lung abrogates experimental asthma by altering dendritic cell function. J. Clin. Invest. 2006, 116, 2935-2944.
169. Puneet, P.; Yap, C.T.; Wong, L.; Lam, Y.; Koh, D.R.; Moochhala, S.; Pfeilschifter, J.; Huwiler, A.; Melendez, A.J. SphK1 regulates proinflammatory responses associated with endotoxin and polymicrobial sepsis. Science 2010, 328, 1290-1294.
170. Xia, P.; Gamble, J.R.; Rye, K.A.; Wang, L.; Hii, C.S.; Cockerill, P.; Khew-Goodall, Y.; Bert, A.G.; Barter, P.J.; Vadas, M.A. Tumor necrosis factor-alpha induces adhesion molecule expression through the sphingosine kinase pathway. Proc. Natl. Acad. Sci. USA 1998, 95, 14196-14201.
171. Pettus, B.J.; Bielawski, J.; Porcelli, A.M.; Reames, D.L.; Johnson, K.R.; Morrow, J.; Chalfant, C.E.; Obeid, L.M.; Hannun, Y.A. The sphingosine kinase 1/sphingosine-1-phosphate pathway mediates COX-2 induction and PGE2 production in response to TNF-alpha. FASEB J. 2003, 17, 1411-1421.
172. Billich, A.; Bornancin, F.; Mechtcheriakova, D.; Natt, F.; Huesken, D.; Baumruker, T. Basal and induced sphingosine kinase 1 activity in A549 carcinoma cells: Function in cell survival and IL-1beta and TNF-alpha induced production of inflammatory mediators. Cell. Signal. 2005, 17, 1203-1217.
173. Alvarez, S.E.; Milstien, S.; Spiegel, S. Autocrine and paracrine roles of sphingosine-1-phosphate. Trends Endocrinol. Metab. TEM 2007, 18, 300-307.
174. Shida, D.; Takabe, K.; Kapitonov, D.; Milstien, S.; Spiegel, S. Targeting SphK1 as a new strategy against cancer. Curr. Drug Targets 2008, 9, 662-673.
175. Liu, H.; Toman, R.E.; Goparaju, S.K.; Maceyka, M.; Nava, V.E.; Sankala, H.; Payne, S.G.; Bektas, M.; Ishii, I.; Chun, J.; et al. Sphingosine kinase type 2 is a putative BH3-only protein that induces apoptosis. J. Biol. Chem. 2003, 278, 40330-40336.
176. Maceyka, M.; Sankala, H.; Hait, N.C.; Le Stunff, H.; Liu, H.; Toman, R.; Collier, C.; Zhang, M.; Satin, L.S.; Merrill, A.H., Jr.; et al. SphK1 and SphK2, sphingosine kinase isoenzymes with opposing functions in sphingolipid metabolism. J. Biol. Chem. 2005, 280, 37118-37129.
177. Paugh, B.S.; Paugh, S.W.; Bryan, L.; Kapitonov, D.; Wilczynska, K.M.; Gopalan, S.M.; Rokita, H.; Milstien, S.; Spiegel, S.; Kordula, T. EGF regulates plasminogen activator inhibitor-1 (PAI-1) by a pathway involving c-Src, PKCdelta, and sphingosine kinase 1 in glioblastoma cells. FASEB J. 2008, 22, 455-465.
178. Xia, P.; Gamble, J.R.; Wang, L.; Pitson, S.M.; Moretti, P.A.; Wattenberg, B.W.; D'Andrea, R.J.; Vadas, M.A. An oncogenic role of sphingosine kinase. Curr. Biol. CB 2000, 10, 1527-1530.
179. Shu, X.; Wu, W.; Mosteller, R.D.; Broek, D. Sphingosine kinase mediates vascular endothelial growth factor-induced activation of ras and mitogen-activated protein kinases. Mol. Cell. Biol. 2002, 22, 7758-7768.
180. French, K.J.; Schrecengost, R.S.; Lee, B.D.; Zhuang, Y.; Smith, S.N.; Eberly, J.L.; Yun, J.K.; Smith, C.D. Discovery and evaluation of inhibitors of human sphingosine kinase. Cancer Res. 2003, 63, 5962-5969.
181. Johnson, K.R.; Johnson, K.Y.; Crellin, H.G.; Ogretmen, B.; Boylan, A.M.; Harley, R.A.; Obeid, L.M. Immunohistochemical distribution of sphingosine kinase 1 in normal and tumor lung tissue. J. Histochem. Cytochem. 2005, 53, 1159-1166.
182. Kohno, M.; Momoi, M.; Oo, M.L.; Paik, J.H.; Lee, Y.M.; Venkataraman, K.; Ai, Y.; Ristimaki, A.P.; Fyrst, H.; Sano, H.; et al. Intracellular role for sphingosine kinase 1 in intestinal adenoma cell proliferation. Mol. Cell. Biol. 2006, 26, 7211-7223.
183. Paugh, S.W.; Paugh, B.S.; Rahmani, M.; Kapitonov, D.; Almenara, J.A.; Kordula, T.; Milstien, S.; Adams, J.K.; Zipkin, R.E.; Grant, S.; et al. A selective sphingosine kinase 1 inhibitor integrates multiple molecular therapeutic targets in human leukemia. Blood 2008, 112, 1382-1391.
184. Kapitonov, D.; Allegood, J.C.; Mitchell, C.; Hait, N.C.; Almenara, J.A.; Adams, J.K.; Zipkin, R.E.; Dent, P.; Kordula, T.; Milstien, S.; et al. Targeting sphingosine kinase 1 inhibits Akt signaling, induces apoptosis, and suppresses growth of human glioblastoma cells and xenografts. Cancer Res. 2009, 69, 6915-6923.
185. French, K.J.; Zhuang, Y.; Maines, L.W.; Gao, P.; Wang, W.; Beljanski, V.; Upson, J.J.; Green, C.L.; Keller, S.N.; Smith, C.D. Pharmacology and antitumor activity of ABC294640, a selective inhibitor of sphingosine kinase-2. J. Pharmacol. Exp. Ther. 2010, 333, 129-139.
186. Salas, A.; Ponnusamy, S.; Senkal, C.E.; Meyers-Needham, M.; Selvam, S.P.; Saddoughi, S.A.; Apohan, E.; Sentelle, R.D.; Smith, C.; Gault, C.R.; et al. Sphingosine kinase-1 and sphingosine 1-phosphate receptor 2 mediate Bcr-Abl1 stability and drug resistance by modulation of protein phosphatase 2A. Blood 2011, 117, 5941-5952.
187. Kim, E.S.; Kim, J.S.; Kim, S.G.; Hwang, S.; Lee, C.H.; Moon, A. Sphingosine 1-phosphate regulates matrix metalloproteinase-9 expression and breast cell invasion through S1P3-Galphaq coupling. J. Cell. Sci. 2011, 124, 2220-2230.
188. Anelli, V.; Gault, C.R.; Snider, A.J.; Obeid, L.M. Role of sphingosine kinase-1 in paracrine/ transcellular angiogenesis and lymphangiogenesis in vitro. FASEB J. 2010, 24, 2727-2738.
189. Lee, H.; Deng, J.; Kujawski, M.; Yang, C.; Liu, Y.; Herrmann, A.; Kortylewski, M.; Horne, D.; Somlo, G.; Forman, S.; et al. STAT3-induced S1PR1 expression is crucial for persistent STAT3 activation in tumors. Nat. Med. 2010, 16, 1421-1428.
190. Liang, J.; Nagahashi, M.; Kim, E.Y.; Harikumar, K.B.; Yamada, A.; Huang, W.C.; Hait, N.C.; Allegood, J.C.; Price, M.M.; Avni, D.; et al. Sphingosine-1-phosphate links persistent STAT3 activation, chronic intestinal inflammation, and development of colitis-associated cancer. Cancer Cell 2013, 23, 107-120.
191. Visentin, B.; Vekich, J.A.; Sibbald, B.J.; Cavalli, A.L.; Moreno, K.M.; Matteo, R.G.; Garland, W.A.; Lu, Y.; Yu, S.; Hall, H.S.; et al. Validation of an anti-sphingosine-1-phosphate antibody as a potential therapeutic in reducing growth, invasion, and angiogenesis in multiple tumor lineages. Cancer Cell 2006, 9, 225-238.
192. LaMontagne, K.; Littlewood-Evans, A.; Schnell, C.; O'Reilly, T.; Wyder, L.; Sanchez, T.; Probst, B.; Butler, J.; Wood, A.; Liau, G.; et al. Antagonism of sphingosine-1-phosphate receptors by FTY720 inhibits angiogenesis and tumor vascularization. Cancer Res. 2006, 66, 221-231.
193. Takabe, K.; Yamada, A.; Rashid, O.; Adams, B.; Huang, W.; Aoyagi, T.; Nagahashi, M. Twofer anti-vascular therapy targeting sphingosine-1-phosphate for breast cancer. Gland Surg. 2012, 1, 80-83.
194. Aoyagi, T.; Nagahashi, M.; Yamada, A.; Takabe, K. The role of sphingosine-1-phosphate in breast cancer tumor-induced lymphangiogenesis. Lymphat. Res. Biol. 2012, 10, 97-106.
195. Yoon, C.M.; Hong, B.S.; Moon, H.G.; Lim, S.; Suh, P.G.; Kim, Y.K.; Chae, C.B.; Gho, Y.S. Sphingosine-1-phosphate promotes lymphangiogenesis by stimulating S1P1/Gi/PLC/Ca2+ signaling pathways. Blood 2008, 112, 1129-1138.
196. Lee, M.J.; Thangada, S.; Claffey, K.P.; Ancellin, N.; Liu, C.H.; Kluk, M.; Volpi, M.; Sha'afi, R.I.; Hla, T. Vascular endothelial cell adherens junction assembly and morphogenesis induced by sphingosine-1-phosphate. Cell 1999, 99, 301-312.
197. Lee, O.H.; Kim, Y.M.; Lee, Y.M.; Moon, E.J.; Lee, D.J.; Kim, J.H.; Kim, K.W.; Kwon, Y.G. Sphingosine 1-phosphate induces angiogenesis: Its angiogenic action and signaling mechanism in human umbilical vein endothelial cells. Biochem. Biophys. Res. Commun. 1999, 264, 743-750.
198. Jang, C.; Koh, Y.J.; Lim, N.K.; Kang, H.J.; Kim, D.H.; Park, S.K.; Lee, G.M.; Jeon, C.J.; Koh, G.Y. Angiopoietin-2 exocytosis is stimulated by sphingosine-1-phosphate in human blood and lymphatic endothelial cells. Arterioscler. Thromb. Vasc. Biol. 2009, 29, 401-407.
199. Nagahashi, M.; Ramachandran, S.; Kim, E.Y.; Allegood, J.C.; Rashid, O.M.; Yamada, A.; Zhao, R.; Milstien, S.; Zhou, H.; Spiegel, S.; et al. Sphingosine-1-phosphate produced by sphingosine kinase 1 promotes breast cancer progression by stimulating angiogenesis and lymphangiogenesis. Cancer Res. 2012, 72, 726-735.
200. Mumprecht, V.; Honer, M.; Vigl, B.; Proulx, S.T.; Trachsel, E.; Kaspar, M.; Banziger-Tobler, N.E.; Schibli, R.; Neri, D.; Detmar, M. In vivo imaging of inflammation and tumor-induced lymph node lymphangiogenesis by immuno-positron emission tomography. Cancer Res. 2010, 70, 8842-8851.
201. Edge, S.B.; Compton, C.C. The American Joint Committee on Cancer: The 7th edition of the AJCC cancer staging manual and the future of TNM. Ann. Surg. Oncol. 2010, 17, 1471-1474.
202. Mizugishi, K.; Yamashita, T.; Olivera, A.; Miller, G.F.; Spiegel, S.; Proia, R.L. Essential role for sphingosine kinases in neural and vascular development. Mol. Cell. Biol.2005, 25, 11113-11121.
203. Zemann, B.; Urtz, N.; Reuschel, R.; Mechtcheriakova, D.; Bornancin, F.; Badegruber, R.; Baumruker, T.; Billich, A. Normal neutrophil functions in sphingosine kinase type 1 and 2 knockout mice. Immunol. Lett. 2007, 109, 56-63.
204. Jung, B.; Obinata, H.; Galvani, S.; Mendelson, K.; Ding, B.S.; Skoura, A.; Kinzel, B.; Brinkmann, V.; Rafii, S.; Evans, T.; et al. Flow-regulated endothelial S1P receptor-1 signaling sustains vascular development. Dev. Cell 2012, 23, 600-610.
205. Gaengel, K.; Niaudet, C.; Hagikura, K.; Lavina, B.; Muhl, L.; Hofmann, J.J.; Ebarasi, L.; Nystrom, S.; Rymo, S.; Chen, L.L.; et al. The sphingosine-1-phosphate receptor S1PR1 restricts sprouting angiogenesis by regulating the interplay between VE-cadherin and VEGFR2. Dev. Cell 2012, 23, 587-599.
206. Ben Shoham, A.; Malkinson, G.; Krief, S.; Shwartz, Y.; Ely, Y.; Ferrara, N.; Yaniv, K.; Zelzer, E. S1P1 inhibits sprouting angiogenesis during vascular development. Development 2012, 139, 3859-3869.
207. Mendelson, K.; Zygmunt, T.; Torres-Vazquez, J.; Evans, T.; Hla, T. Sphingosine 1-phosphate receptor signaling regulates proper embryonic vascular patterning. J. Biol. Chem. 2013, 288, 2143-2156.