Hypoxia-inducible factors and sphingosine 1-phosphate signaling

Anti-Cancer Agents in Medicinal Chemistry

Volumn 11, Issue 9, 2011, Pages 854-862

  Cuvillier, Olivie ^a   Ader, Isabelle ^b  

^a INSTITUT DE PHARMACOLOGIE ET DE BIOLOGIE STRUCTURALE   (France)

^b UNIVERSITÉ PAUL SABATIER   (France)

Author keywords

Cancer therapy; Hypoxia; Hypoxia inducible factor; Sphingosine 1 phosphate; Sphingosine kinase 1

Indexed keywords

2 AMINO 2 (3 OCTYLPHENYLCARBAMOYL)ETHYL PHOSPHATE; 4 (2,6 DICHLORO 4 PYRIDINYL) 1 (1,3 DIMETHYL 4 ISOPROPYL 1H PYRAZOLO[3,4 B]PYRIDIN 6 YL)SEMICARBAZIDE; 5 (4 PHENYL 5 TRIFLUOROMETHYL 2 THIENYL) 3 (3 TRIFLUOROMETHYLPHENYL) 1,2,4 OXADIAZOLE; BENZYLOXYCARBONYLLEUCYLLEUCYLLEUCINAL; CYCLOPHOSPHAMIDE; DAUNORUBICIN; DOXORUBICIN; FINGOLIMOD; HYPOXIA INDUCIBLE FACTOR 1ALPHA; HYPOXIA INDUCIBLE FACTOR 2ALPHA; PREDNISONE; RITUXIMAB; SPHINGOSINE 1 PHOSPHATE; SPHINGOSINE KINASE 1; TOPOTECAN; VINCRISTINE SULFATE;

ADAPTATION; ANGIOGENESIS; B CELL LYMPHOMA; CANCER RESISTANCE; CELL HYPOXIA; CELL PROLIFERATION; CELL SURVIVAL; CHRONIC LYMPHATIC LEUKEMIA; CHRONIC MYELOID LEUKEMIA; GENE EXPRESSION; HEMATOLOGIC MALIGNANCY; HODGKIN DISEASE; HUMAN; LEUKEMIA; LYMPHOMA; METASTASIS; NONHUMAN; REVIEW; SIGNAL TRANSDUCTION; SOLID TUMOR; TUMOR GROWTH;

EID: 80054085425     PISSN: 18715206     EISSN: 18755992     Source Type: Journal    
DOI: 10.2174/187152011797655050     Document Type: Review

References (115)

1. Bazan, N. G.; Placios-Pelaez, R.; Lukiw, W. J., Hypoxia signaling to genes: significance in Alzheimer's disease. Mol. Neurobiol., 2002, 26 (2-3), 283-298.
2. Bergeron, M.; Yu, A. Y.; Solway, K. E.; Semenza, G. L.; Sharp, F. R., Induction of hypoxia-inducible factor-1 (HIF-1) and its target genes following focal ischaemia in rat brain. Eur. J. Neurosci., 1999, 11 (12), 4159-4170.
3. Dachs, G. U.; Patterson, A. V.; Firth, J. D.; Ratcliffe, P. J.; Townsend, K. M.; Stratford, I. J.; Harris, A. L., Targeting gene expression to hypoxic tumor cells. Nat. Med., 1997, 3 (5), 515-520.
4. Maxwell, P. H.; Dachs, G. U.; Gleadle, J. M.; Nicholls, L. G.; Harris, A. L.; Stratford, I. J.; Hankinson, O.; Pugh, C. W.; Ratcliffe, P. J., Hypoxia-inducible factor-1 modulates gene expression in solid tumors and influences both angiogenesis and tumor growth. Proc. Natl. Acad. Sci. U S A, 1997, 94 (15), 8104-8109.
5. Carmeliet, P.; Dor, Y.; Herbert, J. M.; Fukumura, D.; Brusselmans, K.; Dewerchin, M.; Neeman, M.; Bono, F.; Abramovitch, R.; Maxwell, P.; Koch, C. J.; Ratcliffe, P.; Moons, L.; Jain, R. K.; Collen, D.; Keshert, E., Role of HIF-1alpha in hypoxia-mediated apoptosis, cell proliferation and tumour angiogenesis. Nature, 1998, 394 (669, 485-490.
6. Zhong, H.; De Marzo, A. M.; Laughner, E.; Lim, M.; Hilton, D. A.; Zagzag, D.; Buechler, P.; Isaacs, W. B.; Semenza, G. L.; Simons, J. W., Overexpression of hypoxia-inducible factor 1alpha in common human cancers and their metastases. Cancer Res., 1999, 59 (22), 5830-5835.
7. Acker, T.; Acker, H., Cellular oxygen sensing need in CNS function: physiological and pathological implications. J. Exp. Biol., 2004, 207 (Pt 18), 3171-3188.
8. Jain, R. K., Normalization of tumor vasculature: an emerging concept in antiangiogenic therapy. Science, 2005, 307 (5706), 58-62.
9. Vaupel, P.; Mayer, A., Hypoxia in cancer: significance and impact on clinical outcome. Cancer Metastasis Rev., 2007, 26 (2), 225-239.
10. Semenza, G. L., Hypoxia-inducible factor 1 and cancer pathogenesis. IUBMB Life, 2008, 60 (9), 591-597.
11. Vaupel, P., The role of hypoxia-induced factors in tumor progression. Oncologist, 2004, 9 Suppl 5, 10-17.
12. Milosevic, M.; Fyles, A.; Hedley, D.; Hill, R., The human tumor microenvironment: invasive (needle) measurement of oxygen and interstitial fluid pressure. Semin. Radiat. Oncol., 2004, 14 (3), 249-258.
13. Semenza, G. L., Hypoxia-inducible factor 1 (HIF-1) pathway. Sci. STKE, 2007, 2007 (407), cm8.
14. Majmundar, A. J.; Wong, W. J.; Simon, M. C., Hypoxia-inducible factors and the response to hypoxic stress. Mol. Cell, 2010, 40 (2), 294-309.
15. Jaakkola, P.; Mole, D. R.; Tian, Y. M.; Wilson, M. I.; Gielbert, J.; Gaskell, S. J.; Kriegsheim, A.; Hebestreit, H. F.; Mukherji, M.; Schofield, C. J.; Maxwell, P. H.; Pugh, C. W.; Ratcliffe, P. J., Targeting of HIF-alpha to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation. Science, 2001, 292 (5516), 468-472.
16. Maxwell, P. H.; Wiesener, M. S.; Chang, G. W.; Clifford, S. C.; Vaux, E. C.; Cockman, M. E.; Wykoff, C. C.; Pugh, C. W.; Maher, E. R.; Ratcliffe, P. J., The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis. Nature, 1999, 399 (6733), 271-275.
17. Kaelin, W. G., Jr.; Ratcliffe, P. J., Oxygen sensing by metazoans: the central role of the HIF hydroxylase pathway. Mol. Cell, 2008, 30 (4), 393-402.
18. Giaccia, A.; Siim, B. G.; Johnson, R. S., HIF-1 as a target for drug development. Nat. Rev. Drug Discov., 2003, 2 (10), 803-811.
19. Gordan, J. D.; Simon, M. C., Hypoxia-inducible factors: central regulators of the tumor phenotype. Curr. Opin. Genet. Dev., 2007, 17 (1), 71-77.
20. Semenza, G. L., Defining the role of hypoxia-inducible factor 1 in cancer biology and therapeutics. Oncogene, 2010, 29 (5), 625-634.
21. Liao, D.; Corle, C.; Seagroves, T. N.; Johnson, R. S., Hypoxiainducible factor-1alpha is a key regulator of metastasis in a transgenic model of cancer initiation and progression. Cancer Res., 2007, 67 (2), 563-572.
22. Zhang, H.; Qian, D. Z.; Tan, Y. S.; Lee, K.; Gao, P.; Ren, Y. R.; Rey, S.; Hammers, H.; Chang, D.; Pili, R.; Dang, C. V.; Liu, J. O.; Semenza, G. L., Digoxin and other cardiac glycosides inhibit HIF- 1alpha synthesis and block tumor growth. Proc. Natl. Acad. Sci. U S A, 2008, 105 (50), 19579-19586.
23. Lee, K.; Qian, D. Z.; Rey, S.; Wei, H.; Liu, J. O.; Semenza, G. L., Anthracycline chemotherapy inhibits HIF-1 transcriptional activity and tumor-induced mobilization of circulating angiogenic cells. Proc. Natl. Acad. Sci. U S A, 2009, 106 (7), 2353-2358.
24. Melillo, G., Targeting hypoxia cell signaling for cancer therapy. Cancer Metastasis Rev., 2007, 26 (2), 341-352.
25. Spiegel, S.; Milstien, S., Sphingosine-1-phosphate: an enigmatic signalling lipid. Nat. Rev. Mol. Cell. Biol., 2003, 4 (5), 397-407.
26. Ogretmen, B.; Hannun, Y. A., Biologically active sphingolipids in cancer pathogenesis and treatment. Nat. Rev. Cancer, 2004, 4 (8), 604-616.
27. Cuvillier, O., Sphingosine in apoptosis signaling. Biochim. Biophys. Acta., 2002, 1585, 153-162.
28. Hait, N. C.; Allegood, J.; Maceyka, M.; Strub, G. M.; Harikumar, K. B.; Singh, S. K.; Luo, C.; Marmorstein, R.; Kordula, T.; Milstien, S.; Spiegel, S., Regulation of histone acetylation in the nucleus by sphingosine-1-phosphate. Science, 2009, 325 (5945), 1254-1257.
29. Cuvillier, O.; Pirianov, G.; Kleuser, B.; Vanek, P. G.; Coso, O. A.; Gutkind, S.; Spiegel, S., Suppression of ceramide-mediated programmed cell death by sphingosine-1-phosphate. Nature, 1996, 381 (6585), 800-803.
30. Alvarez, S. E.; Milstien, S.; Spiegel, S., Autocrine and paracrine roles of sphingosine-1-phosphate. Trends Endocrinol. Metab., 2007, 18 (8), 300-307.
31. 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. 2000, 10 (23), 1527-1530.
32. Cuvillier, O.; Ader, I.; Bouquerel, P.; Brizuela, L.; Malavaud, B.; Mazerolles, C.; Rischmann, P., Activation of Sphingosine Kinase-1 in Cancer: Implications for Therapeutic Targeting. Curr. Mol. Pharmacol., 2010, 3, 53-65.
33. Malavaud, B.; Pchejetski, D.; Mazerolles, C.; de Paiva, G. R.; Calvet, C.; Doumerc, N.; Pitson, S.; Rischmann, P.; Cuvillier, O., Sphingosine kinase-1 activity and expression in human prostate cancer resection specimens. Eur. J. Cancer, 2010, 46 (18), 3417-3424.
34. Cuvillier, O., Downregulating sphingosine kinase-1 for cancer therapy. Expert Opin. Ther. Targets, 2008, 12 (8), 1009-1020.
35. Karliner, J. S.; Honbo, N.; Summers, K.; Gray, M. O.; Goetzl, E. J., The lysophospholipids sphingosine-1-phosphate and lysophosphatidic acid enhance survival during hypoxia in neonatal rat cardiac myocytes. J. Mol. Cell Cardiol. 2001, 33 (9), 1713-1717.
36. Zhang, J.; Honbo, N.; Goetzl, E. J.; Chatterjee, K.; Karliner, J. S.; Gray, M. O., Signals from type 1 sphingosine 1-phosphate receptors enhance adult mouse cardiac myocyte survival during hypoxia. Am. J. Physiol. Heart Circ. Physiol., 2007, 293 (5), H3150-H3158.
37. Tao, R.; Zhang, J.; Vessey, D. A.; Honbo, N.; Karliner, J. S., Deletion of the sphingosine kinase-1 gene influences cell fate during hypoxia and glucose deprivation in adult mouse cardiomyocytes. Cardiovasc. Res., 2007, 74 (1), 56-63.
38. Yun, J. K.; Kester, M., Regulatory role of sphingomyelin metabolites in hypoxia-induced vascular smooth muscle cell proliferation. Arch. Biochem. Biophys., 2002, 408 (1), 78-86.
39. Ahmad, M.; Long, J. S.; Pyne, N. J.; Pyne, S., The effect of hypoxia on lipid phosphate receptor and sphingosine kinase expression and mitogen-activated protein kinase signaling in human pulmonary smooth muscle cells. Prostaglandins Other. Lipid Mediat., 2006, 79 (3-4), 278-286.
40. Michaud, M. D.; Robitaille, G. A.; Gratton, J. P.; Richard, D. E., Sphingosine-1-phosphate: a novel nonhypoxic activator of hypoxia-inducible factor-1 in vascular cells. Arterioscler. Thromb. Vasc. Biol., 2009, 29 (6), 902-908.
41. Tang, N.; Wang, L.; Esko, J.; Giordano, F. J.; Huang, Y.; Gerber, H. P.; Ferrara, N.; Johnson, R. S., Loss of HIF-1alpha in endothelial cells disrupts a hypoxia-driven VEGF autocrine loop necessary for tumorigenesis. Cancer Cell, 2004, 6 (5), 485-495.
42. Sanchez, T.; Skoura, A.; Wu, M. T.; Casserly, B.; Harrington, E. O.; Hla, T., Induction of vascular permeability by the sphingosine- 1-phosphate receptor-2 (S1P2R) and its downstream effectors ROCK and PTEN. Arterioscler. Thromb. Vasc. Biol., 2007, 27 (6), 1312-1318.
43. Skoura, A.; Sanchez, T.; Claffey, K.; Mandala, S. M.; Proia, R. L.; Hla, T., Essential role of sphingosine 1-phosphate receptor 2 in pathological angiogenesis of the mouse retina. J. Clin. Invest., 2007, 117 (9), 2506-2516.
44. Ader, I.; Brizuela, L.; Bouquerel, P.; Malavaud, B.; Cuvillier, O., Sphingosine kinase 1: a new modulator of hypoxia inducible factor 1alpha during hypoxia in human cancer cells. Cancer Res., 2008, 68 (20), 8635-8642.
45. Skuli, N.; Monferran, S.; Delmas, C.; Lajoie-Mazenc, I.; Favre, G.; Toulas, C.; Cohen-Jonathan-Moyal, E., Activation of RhoB by hypoxia controls hypoxia-inducible factor-1alpha stabilization through glycogen synthase kinase-3 in U87 glioblastoma cells. Cancer Res., 2006, 66 (1), 482-489.
46. Gonzalez, E.; Kou, R.; Michel, T., Rac1 modulates sphingosine 1- phosphate-mediated activation of phosphoinositide 3-kinase/Akt signaling pathways in vascular endothelial cells. J. Biol. Chem., 2006, 281 (6), 3210-3216.
47. Wang, G. L.; Jiang, B. H.; Rue, E. A.; Semenza, G. L., Hypoxiainducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension. Proc. Natl. Acad. Sci. U S A, 1995, 92 (12), 5510-5514.
48. Koh, M. Y.; Darnay, B. G.; Powis, G., Hypoxia-associated factor, a novel E3-ubiquitin ligase, binds and ubiquitinates hypoxiainducible factor 1alpha, leading to its oxygen-independent degradation. Mol. Cell. Biol., 2008, 28 (23), 7081-7095.
49. Cho, S. Y.; Lee, H. J.; Jeong, S. J.; Kim, H. S.; Chen, C. Y.; Lee, E. O.; Kim, S. H., Sphingosine kinase 1 pathway is involved in melatonin-induced HIF-1alpha inactivation in hypoxic PC-3 prostate cancer cells. J. Pineal. Res., 2011, 51, 87-93.
50. Wiesener, M. S.; Jurgensen, J. S.; Rosenberger, C.; Scholze, C. K.; Horstrup, J. H.; Warnecke, C.; Mandriota, S.; Bechmann, I.; Frei, U. A.; Pugh, C. W.; Ratcliffe, P. J.; Bachmann, S.; Maxwell, P. H.; Eckardt, K. U., Widespread hypoxia-inducible expression of HIF- 2alpha in distinct cell populations of different organs. FASEB. J., 2003, 17 (2), 271-273.
51. Kaelin, W. G., Jr., Kidney cancer: now available in a new flavor. Cancer Cell, 2008, 14 (6), 423-424.
52. Gordan, J. D.; Lal, P.; Dondeti, V. R.; Letrero, R.; Parekh, K. N.; Oquendo, C. E.; Greenberg, R. A.; Flaherty, K. T.; Rathmell, W. K.; Keith, B.; Simon, M. C.; Nathanson, K. L., HIF-alpha effects on c-Myc distinguish two subtypes of sporadic VHL-deficient clear cell renal carcinoma. Cancer Cell, 2008, 14 (6), 435-446.
53. Anelli, V.; Gault, C. R.; Cheng, A. B.; Obeid, L. M., Sphingosine Kinase 1 Is Up-regulated during Hypoxia in U87MG Glioma Cells. J. Biol. Chem., 2008, 283 (6), 3365-3375.
54. Wacker, B. K.; Park, T. S.; Gidday, J. M., Hypoxic preconditioninginduced cerebral ischemic tolerance: role of microvascular sphingosine kinase 2. Stroke, 2009, 40 (10), 3342-3348.
55. Schwalm, S.; Doll, F.; Romer, I.; Bubnova, S.; Pfeilschifter, J.; Huwiler, A., Sphingosine kinase-1 is a hypoxia-regulated gene that stimulates migration of human endothelial cells. Biochem. Biophys. Res. Commun., 2008, 368 (4), 1020-1025.
56. Schnitzer, S. E.; Weigert, A.; Zhou, J.; Brune, B., Hypoxia enhances sphingosine kinase 2 activity and provokes sphingosine- 1-phosphate-mediated chemoresistance in A549 lung cancer cells. Mol. Cancer Res., 2009, 7 (3), 393-401.
57. Melillo, G., Hypoxia-inducible factor 1 inhibitors. Methods Enzymol., 2007, 435, 385-402.
58. Pore, N.; Gupta, A. K.; Cerniglia, G. J.; Jiang, Z.; Bernhard, E. J.; Evans, S. M.; Koch, C. J.; Hahn, S. M.; Maity, A., Nelfinavir down-regulates hypoxia-inducible factor 1alpha and VEGF expression and increases tumor oxygenation: implications for radiotherapy. Cancer Res., 2006, 66 (18), 9252-9259.
59. Rapisarda, A.; Uranchimeg, B.; Scudiero, D. A.; Selby, M.; Sausville, E. A.; Shoemaker, R. H.; Melillo, G., Identification of small molecule inhibitors of hypoxia-inducible factor 1 transcriptional activation pathway. Cancer Res., 2002, 62 (15), 4316-4324.
60. Escuin, D.; Kline, E. R.; Giannakakou, P., Both microtubulestabilizing and microtubule-destabilizing drugs inhibit hypoxiainducible factor-1alpha accumulation and activity by disrupting microtubule function. Cancer Res., 2005, 65 (19), 9021-9028.
61. Winkler, F.; Kozin, S. V.; Tong, R. T.; Chae, S. S.; Booth, M. F.; Garkavtsev, I.; Xu, L.; Hicklin, D. J.; Fukumura, D.; di Tomaso, E.; Munn, L. L.; Jain, R. K., Kinetics of vascular normalization by VEGFR2 blockade governs brain tumor response to radiation: role of oxygenation, angiopoietin-1, and matrix metalloproteinases. Cancer Cell, 2004, 6 (6), 553-563.
62. 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.; Kundra, V.; Mills, G. B.; Sabbadini, R. A., Validation of an antisphingosine- 1-phosphate antibody as a potential therapeutic in reducing growth, invasion, and angiogenesis in multiple tumor lineages. Cancer Cell, 2006, 9 (3), 225-238.
63. Chae, S. S.; Paik, J. H.; Furneaux, H.; Hla, T., Requirement for sphingosine 1-phosphate receptor-1 in tumor angiogenesis demonstrated by in vivo RNA interference. J. Clin. Invest., 2004, 114 (8), 1082-1089.
64. LaMontagne, K.; Littlewood-Evans, A.; Schnell, C.; O'Reilly, T.; Wyder, L.; Sanchez, T.; Probst, B.; Butler, J.; Wood, A.; Liau, G.; Billy, E.; Theuer, A.; Hla, T.; Wood, J., Antagonism of sphingosine-1- phosphate receptors by FTY720 inhibits angiogenesis and tumor vascularization. Cancer Res., 2006, 66 (1), 221-231.
65. Herr, B.; Zhou, J.; Werno, C.; Menrad, H.; Namgaladze, D.; Weigert, A.; Dehne, N.; Brune, B., The supernatant of apoptotic cells causes transcriptional activation of hypoxia-inducible factor- 1alpha in macrophages via sphingosine-1-phosphate and transforming growth factor-beta. Blood, 2009, 114 (10), 2140-2148.
66. Hughes, J. E.; Srinivasan, S.; Lynch, K. R.; Proia, R. L.; Ferdek, P.; Hedrick, C. C., Sphingosine-1-phosphate induces an antiinflammatory phenotype in macrophages. Circ. Res., 2008, 102 (8), 950-958.
67. Weigert, A.; Tzieply, N.; von Knethen, A.; Johann, A. M.; Schmidt, H.; Geisslinger, G.; Brune, B., Tumor cell apoptosis polarizes macrophages role of sphingosine-1-phosphate. Mol. Biol. Cell, 2007, 18 (10), 3810-3819.
68. Weis, N.; Weigert, A.; von Knethen, A.; Brune, B., Heme oxygenase-1 contributes to an alternative macrophage activation profile induced by apoptotic cell supernatants. Mol. Biol. Cell, 2009, 20 (5), 1280-1288.
69. Murdoch, C.; Muthana, M.; Coffelt, S. B.; Lewis, C. E., The role of myeloid cells in the promotion of tumour angiogenesis. Nat. Rev. Cancer, 2008, 8 (8), 618-631.
70. Biswas, S. K.; Sica, A.; Lewis, C. E., Plasticity of macrophage function during tumor progression: regulation by distinct molecular mechanisms. J. Immunol., 2008, 180 (4), 2011-2017.
71. Du, W.; Takuwa, N.; Yoshioka, K.; Okamoto, Y.; Gonda, K.; Sugihara, K.; Fukamizu, A.; Asano, M.; Takuwa, Y., S1P(2), the G protein-coupled receptor for sphingosine-1-phosphate, negatively regulates tumor angiogenesis and tumor growth in vivo in mice. Cancer Res., 2010, 70 (2), 772-781.
72. Stewart, M.; Talks, K.; Leek, R.; Turley, H.; Pezzella, F.; Harris, A.; Gatter, K., Expression of angiogenic factors and hypoxia inducible factors HIF 1, HIF 2 and CA IX in non-Hodgkin's lymphoma. Histopathology, 2002, 40 (3), 253-260.
73. Salven, P.; Orpana, A.; Teerenhovi, L.; Joensuu, H., Simultaneous elevation in the serum concentrations of the angiogenic growth factors VEGF and bFGF is an independent predictor of poor prognosis in non-Hodgkin lymphoma: a single-institution study of 200 patients. Blood, 2000, 96 (12), 3712-3718.
74. Niitsu, N.; Okamato, M.; Nakamine, H.; Yoshino, T.; Tamaru, J.; Nakamura, S.; Higashihara, M.; Hirano, M., Simultaneous elevation of the serum concentrations of vascular endothelial growth factor and interleukin-6 as independent predictors of prognosis in aggressive non-Hodgkin's lymphoma. Eur. J. Haematol., 2002, 68 (2), 91-100.
75. Zhao, W. L.; Mourah, S.; Mounier, N.; Leboeuf, C.; Daneshpouy, M. E.; Legres, L.; Meignin, V.; Oksenhendler, E.; Maignin, C. L.; Calvo, F.; Briere, J.; Gisselbrecht, C.; Janin, A., Vascular endothelial growth factor-A is expressed both on lymphoma cells and endothelial cells in angioimmunoblastic T-cell lymphoma and related to lymphoma progression. Lab. Invest., 2004, 84 (11), 1512-1519.
76. Rueda, A.; Olmos, D.; Villareal, V.; Torres, E.; Pajares, B. I.; Alba, E., Elevated vascular endothelial growth factor pretreatment levels are correlated with the tumor burden in Hodgkin lymphoma and continue to be elevated in prolonged complete remission. Clin. Lymphoma Myeloma, 2007, 7 (6), 400-405.
77. Gratzinger, D.; Zhao, S.; Marinelli, R. J.; Kapp, A. V.; Tibshirani, R. J.; Hammer, A. S.; Hamilton-Dutoit, S.; Natkunam, Y., Microvessel density and expression of vascular endothelial growth factor and its receptors in diffuse large B-cell lymphoma subtypes. Am. J. Pathol., 2007, 170 (4), 1362-1369.
78. Kadowaki, I.; Ichinohasama, R.; Harigae, H.; Ishizawa, K.; Okitsu, Y.; Kameoka, J.; Sasaki, T., Accelerated lymphangiogenesis in malignant lymphoma: possible role of VEGF-A and VEGF-C. Br. J. Haematol., 2005, 130 (6), 869-877.
79. Jorgensen, J. M.; Sorensen, F. B.; Bendix, K.; Nielsen, J. L.; Olsen, M. L.; Funder, A. M.; d'Amore, F., Angiogenesis in non-Hodgkin's lymphoma: clinico-pathological correlations and prognostic significance in specific subtypes. Leuk. Lymphoma, 2007, 48 (3), 584-595.
80. Ganjoo, K. N.; Moore, A. M.; Orazi, A.; Sen, J. A.; Johnson, C. S.; An, C. S., The importance of angiogenesis markers in the outcome of patients with diffuse large B cell lymphoma: a retrospective study of 97 patients. J. Cancer Res. Clin. Oncol., 2008, 134 (3), 381-387.
81. Doussis-Anagnostopoulou, I. A.; Talks, K. L.; Turley, H.; Debnam, P.; Tan, D. C.; Mariatos, G.; Gorgoulis, V.; Kittas, C.; Gatter, K. C., Vascular endothelial growth factor (VEGF) is expressed by neoplastic Hodgkin-Reed-Sternberg cells in Hodgkin's disease. J. Pathol., 2002, 197 (5), 677-683.
82. Passam, F. H.; Alexandrakis, M. G.; Moschandrea, J.; Sfiridaki, A.; Roussou, P. A.; Siafakas, N. M., Angiogenic molecules in Hodgkin's disease: results from sequential serum analysis. Int. J. Immunopathol. Pharmacol., 2006, 19 (1), 161-170.
83. Passam, F. H.; Alexandrakis, M. G.; Kafousi, M.; Fotinou, M.; Darivianaki, K.; Tsirakis, G.; Roussou, P. A.; Stathopoulos, E. N.; Siafakas, N. M., Histological expression of angiogenic factors: VEGF, PDGFRalpha, and HIF-1alpha in Hodgkin lymphoma. Pathol. Res. Pract., 2009, 205 (1), 11-20.
84. Giatromanolaki, A.; Koukourakis, M. I.; Pezzella, F.; Sivridis, E.; Turley, H.; Harris, A. L.; Gatter, K. C., Phosphorylated VEGFR2/KDR receptors are widely expressed in B-cell non- Hodgkin's lymphomas and correlate with hypoxia inducible factor activation. Hematol. Oncol., 2008, 26 (4), 219-224.
85. Evens, A. M.; Schumacker, P. T.; Helenowski, I. B.; Singh, A. T.; Dokic, D.; Keswani, A.; Kordeluk, E.; Raji, A.; Winter, J. N.; Jovanovic, B. D.; Holmgren, A.; Nelson, B. P.; Gordon, L. I., Hypoxia inducible factor-alpha activation in lymphoma and relationship to the thioredoxin family. Br. J. Haematol., 2008, 141 (5), 676-680.
86. Evens, A. M.; Sehn, L. H.; Farinha, P.; Nelson, B. P.; Raji, A.; Lu, Y.; Brakman, A.; Parimi, V.; Winter, J. N.; Schumacker, P. T.; Gascoyne, R. D.; Gordon, L. I., Hypoxia-inducible factor-1 {alpha} expression predicts superior survival in patients with diffuse large B-cell lymphoma treated with R-CHOP. J. Clin. Oncol., 2010, 28 (6), 1017-1024.
87. Argyriou, P.; Papageorgiou, S. G.; Panteleon, V.; Psyrri, A.; Bakou, V.; Pappa, V.; Spathis, A.; Economopoulou, P.; Papageorgiou, E.; Economopoulos, T.; Rontogianni, D., Hypoxiainducible factors in mantle cell lymphoma: implication for an activated mTORC1-->HIF-1alpha pathway. Ann. Hematol., 2011, 90 (3), 315-322.
88. Psyrri, A.; Papageorgiou, S.; Liakata, E.; Scorilas, A.; Rontogianni, D.; Kontos, C. K.; Argyriou, P.; Pectasides, D.; Harhalakis, N.; Pappa, V.; Kolialexi, A.; Economopoulou, C.; Kontsioti, F.; Maratou, E.; Dimitriadis, G.; Economopoulou, P.; Economopoulos, T., Phosphatidylinositol 3'-kinase catalytic subunit alpha gene amplification contributes to the pathogenesis of mantle cell lymphoma. Clin. Cancer Res., 2009, 15 (18), 5724-5732.
89. Qiao, Q.; Nozaki, Y.; Sakoe, K.; Komatsu, N.; Kirito, K., NFkappaB mediates aberrant activation of HIF-1 in malignant lymphoma. Exp. Hematol., 2010, 38 (12), 1199-11208.
90. Rius, J.; Guma, M.; Schachtrup, C.; Akassoglou, K.; Zinkernagel, A. S.; Nizet, V.; Johnson, R. S.; Haddad, G. G.; Karin, M., NFkappaB links innate immunity to the hypoxic response through transcriptional regulation of HIF-1alpha. Nature, 2008, 453 (7196), 807-811.
91. 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.; Milstien, S.; Spiegel, S., Sphingosine-1-phosphate is a missing cofactor for the E3 ubiquitin ligase TRAF2. Nature, 2010, 465 (7301), 1084-1088.
92. Perez-Atayde, A. R.; Sallan, S. E.; Tedrow, U.; Connors, S.; Allred, E.; Folkman, J., Spectrum of tumor angiogenesis in the bone marrow of children with acute lymphoblastic leukemia. Am. J. Pathol., 1997, 150 (3), 815-821.
93. Fiedler, W.; Graeven, U.; Ergun, S.; Verago, S.; Kilic, N.; Stockschlader, M.; Hossfeld, D. K., Vascular endothelial growth factor, a possible paracrine growth factor in human acute myeloid leukemia. Blood, 1997, 89 (6), 1870-1875.
94. Hussong, J. W.; Rodgers, G. M.; Shami, P. J., Evidence of increased angiogenesis in patients with acute myeloid leukemia. Blood, 2000, 95 (1), 309-313.
95. Kini, A. R.; Kay, N. E.; Peterson, L. C., Increased bone marrow angiogenesis in B cell chronic lymphocytic leukemia. Leukemia, 2000, 14 (8), 1414-1418.
96. Aguayo, A.; Estey, E.; Kantarjian, H.; Mansouri, T.; Gidel, C.; Keating, M.; Giles, F.; Estrov, Z.; Barlogie, B.; Albitar, M., Cellular vascular endothelial growth factor is a predictor of outcome in patients with acute myeloid leukemia. Blood, 1999, 94 (11), 3717-3721.
97. Molica, S.; Vitelli, G.; Levato, D.; Gandolfo, G. M.; Liso, V., Increased serum levels of vascular endothelial growth factor predict risk of progression in early B-cell chronic lymphocytic leukaemia. Br. J. Haematol., 1999, 107 (3), 605-610.
98. Aguayo, A.; Kantarjian, H.; Manshouri, T.; Gidel, C.; Estey, E.; Thomas, D.; Koller, C.; Estrov, Z.; O'Brien, S.; Keating, M.; Freireich, E.; Albitar, M., Angiogenesis in acute and chronic leukemias and myelodysplastic syndromes. Blood, 2000, 96 (6), 2240-2245.
99. Bellamy, W. T.; Richter, L.; Frutiger, Y.; Grogan, T. M., Expression of vascular endothelial growth factor and its receptors in hematopoietic malignancies. Cancer Res., 1999, 59 (3), 728-733.
100. Keyhani, A.; Jendiroba, D. B.; Freireich, E. J., Angiogenesis and leukemia. Leuk. Res., 2001, 25 (8), 639-645.
101. Wellmann, S.; Guschmann, M.; Griethe, W.; Eckert, C.; von Stackelberg, A.; Lottaz, C.; Moderegger, E.; Einsiedel, H. G.; Eckardt, K. U.; Henze, G.; Seeger, K., Activation of the HIF pathway in childhood ALL, prognostic implications of VEGF. Leukemia, 2004, 18 (5), 926-933.
102. Staller, P.; Sulitkova, J.; Lisztwan, J.; Moch, H.; Oakeley, E. J.; Krek, W., Chemokine receptor CXCR4 downregulated by von Hippel-Lindau tumour suppressor pVHL. Nature, 2003, 425 (6955), 307-311.
103. Rombouts, E. J.; Pavic, B.; Lowenberg, B.; Ploemacher, R. E., Relation between CXCR-4 expression, Flt3 mutations, and unfavorable prognosis of adult acute myeloid leukemia. Blood, 2004, 104 (2), 550-557.
104. Fiegl, M.; Samudio, I.; Clise-Dwyer, K.; Burks, J. K.; Mnjoyan, Z.; Andreeff, M., CXCR4 expression and biologic activity in acute myeloid leukemia are dependent on oxygen partial pressure. Blood, 2009, 113 (7), 1504-1512.
105. Konopleva, M.; Tabe, Y.; Zeng, Z.; Andreeff, M., Therapeutic targeting of microenvironmental interactions in leukemia: mechanisms and approaches. Drug Resist. Updat., 2009, 12 (4-5), 103-113.
106. Yook, Y. J.; Seo, Y. J.; Kang, H. J.; Ko, S. H.; Shin, H. Y.; Lee, J. J.; Jeong, G.; Ahn, H. S., Induction of hypoxia-inducible factor- 1alpha inhibits drug-induced apoptosis in the human leukemic cell line HL-60. Korean J. Hematol., 2010, 45 (3), 158-163.
107. Hatfield, K. J.; Bedringsaas, S. L.; Ryningen, A.; Gjertsen, B. T.; Bruserud, O., Hypoxia increases HIF-1alpha expression and constitutive cytokine release by primary human acute myeloid leukaemia cells. Eur. Cytokine Netw., 2010, 21 (3), 154-164.
108. Zhong, H.; Mabjeesh, N.; Willard, M.; Simons, J., Nuclear expression of hypoxia-inducible factor 1alpha protein is heterogeneous in human malignant cells under normoxic conditions. Cancer Lett., 2002, 181 (2), 233-238.
109. Ghosh, A. K.; Shanafelt, T. D.; Cimmino, A.; Taccioli, C.; Volinia, S.; Liu, C. G.; Calin, G. A.; Croce, C. M.; Chan, D. A.; Giaccia, A. J.; Secreto, C.; Wellik, L. E.; Lee, Y. K.; Mukhopadhyay, D.; Kay, N. E., Aberrant regulation of pVHL levels by microRNA promotes the HIF/VEGF axis in CLL B cells. Blood, 2009, 113 (22), 5568-5574.
110. Mayerhofer, M.; Valent, P.; Sperr, W. R.; Griffin, J. D.; Sillaber, C., BCR/ABL induces expression of vascular endothelial growth factor and its transcriptional activator, hypoxia inducible factor- 1alpha, through a pathway involving phosphoinositide 3-kinase and the mammalian target of rapamycin. Blood, 2002, 100 (10), 3767-3775.
111. Mahon, F. X.; Deininger, M. W.; Schultheis, B.; Chabrol, J.; Reiffers, J.; Goldman, J. M.; Melo, J. V., Selection and characterization of BCR-ABL positive cell lines with differential sensitivity to the tyrosine kinase inhibitor STI571: diverse mechanisms of resistance. Blood, 2000, 96 (3), 1070-1079.
112. Gorre, M. E.; Mohammed, M.; Ellwood, K.; Hsu, N.; Paquette, R.; Rao, P. N.; Sawyers, C. L., Clinical resistance to STI-571 cancer therapy caused by BCR-ABL gene mutation or amplification. Science, 2001, 293 (5531), 876-880.
113. Zhao, F.; Mancuso, A.; Bui, T. V.; Tong, X.; Gruber, J. J.; Swider, C. R.; Sanchez, P. V.; Lum, J. J.; Sayed, N.; Melo, J. V.; Perl, A. E.; Carroll, M.; Tuttle, S. W.; Thompson, C. B., Imatinib resistance associated with BCR-ABL upregulation is dependent on HIF- 1alpha-induced metabolic reprograming. Oncogene, 2010, 29 (20), 2962-2972.
114. Bonhoure, E.; Lauret, A.; Barnes, D. J.; Martin, C.; Malavaud, B.; Kohama, T.; Melo, J. V.; Cuvillier, O., Sphingosine kinase-1 is a downstream regulator of imatinib-induced apoptosis in chronic myeloid leukemia cells. Leukemia, 2008, 22 (5), 971-979.
115. Baran, Y.; Salas, A.; Senkal, C. E.; Gunduz, U.; Bielawski, J.; Obeid, L. M.; Ogretmen, B., Alterations of ceramide/sphingosine 1-phosphate rheostat involved in the regulation of resistance to imatinib-induced apoptosis in K562 human chronic myeloid leukemia cells. J. Biol. Chem., 2007, 282 (15), 10922-10934.