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Mechanisms of angiogenesis in gliomas

  • Clinical–patient studies
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Summary

Gliomas are the most frequent primary tumors of the central nervous system in adults. Glioblastoma multiforme, the most aggressive form of astrocytic tumors, displays a rapid progression that is accompanied by particular poor prognosis of patients. Intense angiogenesis is a distinguishing pathologic characteristic of these tumors and in fact, glioblastomas are of the most highly vascularized malignant tumors. For this reason, research and therapy strategies have focused on understanding the mechanisms leading to the origin of tumor angiogenic blood vessels in order to develop new approaches that effectively block angiogenesis and cause tumor regression. We discuss here some important features of glioma angiogenesis and we present molecules and factors and their possible functions and interactions that play a role in neovascularization. In spite of the great progress that molecular biology has achieved on investigating tumor angiogenesis, many aspects remain obscure and the complexity of the angiogenic process stands for an obstacle in identifying the exact and complete molecular pathways orchestrating new blood vessels formation, which are necessary for the survival and expansion of these tumors.

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References

  1. Yoshida S, Ono M, Shono T, Izumi H, Ishibashi T, Suzuki H, Kuwano M Involvement of interleukin-8, vascular endothelial growth factor, and basic fibroblast growth factor in tumor necrosis factor alpha-dependent angiogenesis Mol Cell Biol 17: 4015–4023, 1997

    PubMed  CAS  Google Scholar 

  2. Folkman J The role of angiogenesis in tumor growth Semin Cancer Biol 3: 65–71, 1992

    PubMed  CAS  Google Scholar 

  3. Louis DN, Pomeroy SL, Gairncross JG Focus on central nervous system neoplasia Cancer Cell 1:125–128, 2002

    Article  PubMed  CAS  Google Scholar 

  4. Kleihues P, Louis DN, Scheithauer BW, Rorke LB, Reifenberger G, Burger PC, Cavenee WK The WHO classification of tumors of the nervous system J Neuropathol Exp Neurol 61 : 215–225, 2002

    PubMed  Google Scholar 

  5. Jansen M, de Witt Hamer PC, Witmer AN, Troost D, van Noorden CJ Current perspectives on antiangiogenesis strategies in the treatment of malignant gliomas Brain Res Rev 45: 146–163, 2004

    Article  CAS  Google Scholar 

  6. Fueyo J, Gomez-Manzano C, Yung WKA, Kyritsis AP The functional role of tumor suppressor genes in gliomas: clues for future therapeutic strategies Neurology 51: 1250–1255, 1998

    PubMed  CAS  Google Scholar 

  7. Prigent SA, Nagane M, Lin H, Huvar I, Boss GR, Feramisco JR, Cavenee WK, Huang HS Enhanced tumorigenic behaviour of glioblastoma cells expressing a truncated epidermal growth factor receptor is mediated through the Ras-Shc-Grb2 pathway J Biol Chem 271: 25639–25645, 1996

    Article  PubMed  CAS  Google Scholar 

  8. Steck PA, Pershouse MA, Jasser SA, Yung WK, Lin H, Ligon AH, Langford LA, Baumgard ML, Hattier T, Davis T, Frye C, Hu R, Swedlund B, Teng DH, Tavtigian SV Identification of a candidate tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers Nat Genet 15: 356–362, 1997

    PubMed  CAS  Google Scholar 

  9. Folkman J What is the evidence that tumors are angiogenesis dependent? J Natl Cancer Inst 82: 4–6, 1990

    PubMed  CAS  Google Scholar 

  10. Leon SP, Folkerth RD, Black PM Microvessel density is a prognostic indicator for patients with astroglial brain tumors Cancer 77: 362–372, 1996

    Article  PubMed  CAS  Google Scholar 

  11. Lamszus K, Kunkel P, Westphal M Invasion as limitation to anti-angiogenic glioma therapy Acta Neurochir Suppl 88: 169–177, 2003

    PubMed  CAS  Google Scholar 

  12. Brat DJ, Van Meir EG Glomeruloid microvascular proliferation orchestrated by VPF/VEGF: new world of angiogenesis research Am J Pathol 158: 789–796, 2001

    PubMed  CAS  Google Scholar 

  13. Wesseling P, Schlingemann RO, Rietveld FJ, Link M, Burger PC, Ruiter DJ Early and extensive contribution of pericytes/vascular smooth muscle cells to microvascular proliferation in glioblastoma multiforme: an immuno-light and immuno-electron microscopic study J Neuropathol Exp Neurol 54: 304–310, 1995

    PubMed  CAS  Google Scholar 

  14. Kaur B, Tan C, Brat DJ, Post DE, Van Meir EG Genetic and hypoxic regulation of angiogenesis in gliomas J Neurooncol 70: 229–243, 2004

    Article  PubMed  Google Scholar 

  15. Pore N, Liu S, Haas-Kogan DA, O’Rourke DM, Maity A PTEN mutation and epidermal growth factor receptor activation regulate vascular endothelial growth factor (VEGF) mRNA expression in human glioblastoma cells by transactivating the proximal VEGF promoter Cancer Res 63: 236–241, 2003

    PubMed  CAS  Google Scholar 

  16. Brat DJ, Van Meir EG Vaso-occlusive and prothrombotic mechanisms associated with tumor hypoxia, necrosis and accelerated growth in glioblastoma Lab Invest 84: 397–405, 2004

    Article  PubMed  CAS  Google Scholar 

  17. 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 284: 1994–1998, 1999

    Article  PubMed  CAS  Google Scholar 

  18. Tse V, Yung Y, Santarelli JG, Juan D, Hsiao M, Haas M, Harsh G 4th, Silrerberg G Effects of tumor suppressor gene (p53) on brain tumor angiogenesis and expression of angiogenenic modulators Anticancer Res 24: 1–10, 2004

    PubMed  CAS  Google Scholar 

  19. Kyritsis AP, Xu R, Bondy M, Levin VA, Bruner JM Correlation of p53 immunoreactivity and sequencing in patients with glioma Mol Carcinog 15: 1–4, 1996

    Article  PubMed  CAS  Google Scholar 

  20. Machein MR, Plate KH VEGF in brain tumors J Neurooncol 50: 109–120, 2000

    Article  PubMed  CAS  Google Scholar 

  21. 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 87: 1161–1169, 1996

    PubMed  CAS  Google Scholar 

  22. Kim I, Kim JH, Ryu YS, Jung SH, Nah JJ, Koh GY Characterization and expression of a novel alternatively spliced human angiopoietin-2 J Biol Chem 275:18550–18556, 2000

    Article  PubMed  CAS  Google Scholar 

  23. Lobov IB, Brooks PC, Lang RA: Angiopoietin-2 displays VEGF-dependent modulation of capillary structure and endothelial cell survival in vivo. Proc Natl Acad Sci USA 99: 11205–11210, 2002

    Google Scholar 

  24. Koga K, Todaka T, Morioka M, Hamada J, Kai Y, Yano S, Okamura A, Takakura N, Suda T, Ushio Y Expression of angiopoietin-2 in human glioma cells and its role for angiogenesis Cancer Res 61: 6248–6254, 2001

    PubMed  CAS  Google Scholar 

  25. Semenza G Signal transduction to hypoxia-inducible factor 1 Biochem Pharmacol 64: 993–998, 2002

    Article  PubMed  CAS  Google Scholar 

  26. Forsythe JA, Jiang BH, Iyer NV, Agani F, Leung SW, Koos RD, Semenza GL Activation of vascular endothelial growth factor gene transcription by hypoxia-inducible factor 1 Mol Cell Biol 16: 4604–4613, 1996

    PubMed  CAS  Google Scholar 

  27. May D, Iin A, Gal O, Kalinski H, Feinstein E, Keshet E Ero1-L alpha plays a key role in a HIF-1-mediated pathway to improve disulfide bond formation VEGF secretion under hypoxia: implication for cancer Oncogene 24: 1011–1020, 2005

    Article  PubMed  CAS  Google Scholar 

  28. Kaur B, Khwaja FW, Severson EA, Matheny SL, Brat DJ, Van Meir EG Hypoxia and the hypoxia-inducible-factor pathway in glioma growth and angiogenesis Neuro-oncol 7: 134–153, 2005

    Article  PubMed  CAS  Google Scholar 

  29. Gomez-Manzano C, Fueyo J, Jiang H, Glass TL, Lee HY, Hu M, Liu JL, Jasti SL, Liu TJ, Conrad CA, Yung WK Mechanisms underlying PTEN regulation of vascular endothelial growth factor and angiogenesis Ann Neurol 53: 109–117, 2003

    Article  PubMed  CAS  Google Scholar 

  30. Bacher M, Schrader J, Thompson N, Kuschela K, Gemsa D, Waeber G, Schlegel J Up-regulation of macrophage migration inhibitory factor gene and protein expression in glial tumor cells during hypoxic and hypoglycemic stress indicates a critical role for angiogenesis in glioblastoma multiforme Am J Pathol 162: 11–17, 2003

    PubMed  CAS  Google Scholar 

  31. Munaut C, Boniver J, Foidart JM, Deprez M Macrophage migration inhibitory factor (MIF) expression in human glioblastomas correlates with vascular endothelial growth factor (VEGF) expression Neuropathol Appl Neurobiol 28: 452–460, 2002

    Article  PubMed  CAS  Google Scholar 

  32. Junker N, Latini S, Petersen LN, Kristjansen PE Expression and regulation patterns of hyaluronidases in small cell lung cancer and glioma lines Oncol Rep 10: 609–616, 2003

    PubMed  CAS  Google Scholar 

  33. Leung DW, Cachianes G, Kuang WJ, Goeddel DV, Ferrara N Vascular endothelial growth factor is a secreted angiogenic mitogen Science 246: 1306–1309, 1989

    PubMed  CAS  Google Scholar 

  34. Machein MR, Plate KH VEGF in brain tumors J Neuro-oncol 50: 109–120, 2000

    Article  CAS  Google Scholar 

  35. Whitaker GB, Limberg BJ, Rosenbaum JS Vascular endothelial growth factor receptor-2 and neuropilin-1 form a receptor complex that is responsible for the differential signaling potency of VEGF(165) and VEGF(121) J Biol Chem 276: 25520–25531, 2001

    Article  PubMed  CAS  Google Scholar 

  36. Wilting J, Birkenhager R, Eichmann A, Kurz H, Martiny-Baron G, Marme D, McCarthy JE, Christ B, Weich HA VEGF121 induces proliferation of vascular endothelial cells and expression of flk-1 without affecting lymphatic vessels of chorioallantoic membrane Dev Biol 176: 76–85, 1996

    Article  PubMed  CAS  Google Scholar 

  37. Barleon B, Siemeister G, Martiny-Baron G, Weindel K, Herzog C, Marme D Vascular endothelial growth factor up-regulates its receptor fms-like tyrosine kinase 1 (FLT-1) and a soluble variant of FLT-1 in human vascular endothelial cells Cancer Res 57: 5421–5425, 1997

    PubMed  CAS  Google Scholar 

  38. Plate KH, Breier G, Weich HA, Risau W Vascular endothelial growth factor is a potential tumour angiogenesis factor in human gliomas in vivo Nature 359: 845–848, 1992

    Article  PubMed  CAS  Google Scholar 

  39. 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 splicingJ Biol Chem 266: 11947–11954, 1991

    PubMed  CAS  Google Scholar 

  40. Zhang L, Yu D, Hu M, Xiong S, Lang A, Ellis LM, Pollock RE Wild-type p53 suppresses angiogenesis in human leiomyosarcoma and synovial sarcoma by transcriptional suppression of vascular endothelial growth factor expression Cancer Res 60:3655–3661, 2000

    PubMed  CAS  Google Scholar 

  41. Mukhopadhyay D, Knebelmann B, Cohen HT, Ananth S, Sukhatme VP The Von Hippel-Lindau tumor suppressor gene product interacts with Sp1 to repress vascular endothelial growth factor promoter activity Mol Cell Biol 17: 5629–5639,1997

    PubMed  CAS  Google Scholar 

  42. Jiang BH, Zheng JZ, Aoki M, Vogt PK Phosphatidylinositol 3-kinase signaling mediates angiogenesis and expression of vascular endothelial growth factor in endothelial cells Proc Natl Acad Sci USA 97: 1749–1753, 2000

    Article  PubMed  CAS  Google Scholar 

  43. Woods SA, McGlade CJ, Guha A Phosphatidylinositol 3-kinase and MAPK/ERK kinase 1/2 differential regulate expression of vascular endothelial growth factor in human malignant astrocytoma cells Neuro-oncol 4: 242–252, 2002

    Article  PubMed  CAS  Google Scholar 

  44. Maity A, Pore N, Lee J, Solomon D, O’Rourke DM Epidermal growth factor receptor transcriptionally up-regulates vascular endothelial growth factor expression in human glioblastoma cells via a pathway involving phosphatidylinositol 3′-kinase and distinct from that induced by hypoxia Cancer Res 60: 5879–5886, 2000

    PubMed  CAS  Google Scholar 

  45. Huang S, Pettaway CA, Uehara H, Bucana CD, Fidler IJ Blockade of NF-kappaB activity in human prostate cancer cells is associated with suppression of angiogenesis, invasion and metastasis Oncogene 20: 4188–4197, 2001

    Article  PubMed  CAS  Google Scholar 

  46. Wu JL, Abe T, Inoue A, Fujiki M, Kobayashi H IkappaBalphaM suppresses angiogenesis and tumorigenesis promoted by a constitutively active mutant EGFR in human glioma cells Neurol Res 26: 785–791, 2004

    Article  PubMed  CAS  Google Scholar 

  47. Kimba Y, Abe T, Wu JL, Inoue R, Fukiki M, Kohno K, Kobayashi H Mutant IkappaBalpha suppresses hypoxia-induced VEGF expression through downregulation of HIF-1alpha and COX-2 in human glioma cells Oncol Res 15: 139–149, 2005

    PubMed  CAS  Google Scholar 

  48. Saino M, Maruyama T, Sekiya T, Kayama T, Murakami Y Inhibition of angiogenesis in human glioma cell lines by antisense RNA from the soluble guanylate cyclase genes, GUCY1A3 and GUCY1B3 Oncol Rep 12: 47–52, 2004

    PubMed  CAS  Google Scholar 

  49. Tsai JC, Goldman CK, Gillespie GY Vascular endothelial growth factor in human glioma cell lines: induced secretion by EGF, PDGF-BB and bFGF J Neurosurg 82: 864–873, 1995

    PubMed  CAS  Google Scholar 

  50. Guo P, Hu B, Gu W, Xu L, Wang D, Huang HJ, Cavenee WK, Cheng SY Platelet-derived growth factor-B enhances glioma angiogenesis by stimulating vascular endothelial growth factor expression in tumor endothelia and by promoting pericyte recruitment Am J Pathol 162: 1083–1093, 2003

    PubMed  CAS  Google Scholar 

  51. Wang D, Huang HJ, Kazlauskas A, Cavenee WK Induction of vascular endothelial growth factor expression in endothelial cells by platelet-derived growth factor through the activation of phosphatidylinositol 3-kinase Cancer Res 59: 1464–1472, 1999

    PubMed  CAS  Google Scholar 

  52. Finkenzeller G, Sparacio A, Technau A, Marme D, Siemeister G Sp1 recognition sites in the proximal promoter of the human vascular endothelial growth factor gene are essential for platelet-derived growth factor-induced gene expression Oncogene 15: 669–676, 1997

    Article  PubMed  CAS  Google Scholar 

  53. Deroanne CF, Hajitou A, Calberg-Bacq CM, Nusgens BV, Lapiere CM Angiogenesis by fibroblast growth factor 4 is mediated through an autocrine up-regulation of vascular endothelial growth factor expression Cancer Res 57: 5590–5597, 1997

    PubMed  CAS  Google Scholar 

  54. Goldman CK, Kim J, Wong WL, King V, Brock T, Gillespie GY Epidermal growth factor stimulates vascular endothelial growth factor production by human malignant glioma cells: a model of glioblastoma multiforme pathophysiology Mol Biol Cell 4: 121–133, 1993

    PubMed  CAS  Google Scholar 

  55. Ryuto M, Ono M, Izumi H, Yoshida S, Weich HA, Kohno K, Kuwano M Induction of vascular endothelial growth factor by tumor necrosis factor alpha in human glioma cells Possible roles of SP-1J Biol Chem 271: 28220–28228, 1996

    Article  PubMed  CAS  Google Scholar 

  56. Nabors LB, Suswam E, Huang Y, Yang X, Johnson MJ, King PH Tumor necrosis factor alpha induces angiogenic factor up-regulation in malignant glioma cells: a role for RNA stabilization and HuR Cancer Res 63: 4181–4187, 2003

    PubMed  CAS  Google Scholar 

  57. Koochekpour S, Merzak A, Pilkington GJ Vascular endothelial growth factor production is stimulated by gangliosites and TGF-beta isoforms in human glioma cells in vitro Cancer Lett 102: 209–215, 1996

    Article  PubMed  CAS  Google Scholar 

  58. Cohen T, Nahari D, Cerem LW, Neufeld G, Levi BZ Interleukin 6 induces the expression of vascular endothelial growth factor J Biol Chem 271: 736–741, 1996

    Article  PubMed  CAS  Google Scholar 

  59. Loeffler S, Fayard B, Weis J, Weissenberger J Interleukin-6 induces transcriptional activation of vascular endothelial growth factor (VEGF) in astrocytes in vivo and regulates VEGF promoter activity in glioblastoma cells via direct interaction between STAT3 and Sp1 Int J Cancer 115: 202–213, 2005

    Article  PubMed  CAS  Google Scholar 

  60. Klagsbrun M The fibroblast growth factor family: structural and biological properties Prog Growth Factor Res 1:207–235, 1989

    Article  PubMed  CAS  Google Scholar 

  61. Stefanik DF, Rizkalla LR, Soi A, Goldblatt SA, Rizkalla WM: Acidic and basic fibroblast growth factors are present in glioblastoma multiforme Cancer Res 51: 5760–5765, 1991

    PubMed  CAS  Google Scholar 

  62. Morrison RS, Gross JL, Herblin WF, Reilly TM, Lasala PA, Alterman RL, Moskal JR, Kornblith PL, Dexter DL Basic fibroblast growth factor-like activity and receptors are expressed in a human glioma cell line Cancer Res 50: 2524–2529, 1990

    PubMed  CAS  Google Scholar 

  63. Moscatelli D, Presta M, Rifkin DB Purification of a factor from human placenta that stimulates capillary endothelial cell protease production, DNA synthesis and migration Proc Natl Acad Sci USA 83: 2091–2095, 1986

    PubMed  CAS  Google Scholar 

  64. Dunn IF, Heese O, Black PM Growth factors in glioma angiogenesis: FGFs, PDGF, EGF and TGFs J Neurooncol 50: 121–137, 2000

    Article  PubMed  CAS  Google Scholar 

  65. Qiao D, Meyer K, Mundhenke C, Drew SA, Friedl A Heparan sulphate proteoglycans as regulators of fibroblast growth factor-2 signaling in brain endothelial cells. Specific role for glypican-1 in glioma angiogenesisJ Biol Chem 278: 16045–16053, 2003

    Article  PubMed  CAS  Google Scholar 

  66. Heldin CH, Westermark B Mechanism of action and in vivo role of platelet-derived growth factor Physiol Rev 79: 1283–1316, 1999

    PubMed  CAS  Google Scholar 

  67. Hermanson M, Funa K, Hartman M, Claesson-Welsh L, Heldin CH, Westermark B, Nister M Platelet-derived growth factor and its receptors in human glioma tissue: expression of messenger RNA and protein suggests the presence of autocrine and paracrine loops Cancer Res 52: 3213–3219, 1992

    PubMed  CAS  Google Scholar 

  68. Hermansson M, Nister M, Betsholtz C, Heldin CH, Westermark B, Funa K Endothelial cell hyperplasia in human glioblastoma: coexpression of mRNA for platelet-derived growth factor (PDGF) B chain and PDGF receptor suggests autocrine growth stimulation Proc Natl Acad Sci USA 85: 7748–7752, 1988

    PubMed  CAS  Google Scholar 

  69. Risau W, Drexler H, Mironov V, Smits A, Siegbahn A, Funa K, Heldin CH: Platelet-derived growth factor is angiogenic in vivo Growth Factors 7: 261–266, 1992

    PubMed  CAS  Google Scholar 

  70. Brockmann MA, Ulbricht U, Gruner K, Fillbrandt R, Westphal N, Lamszus K Glioblastoma and cerebral microvascular endothelial cell migration in response to tumor-associated growth factors Neurosurgery 52: 1391–1399, 2003

    Article  PubMed  Google Scholar 

  71. Feldkamp MM, Lau N, Guha A Signal transduction pathways and their relevance in human astrocytomas J Neurooncol 35: 223–248, 1997

    Article  PubMed  CAS  Google Scholar 

  72. Steck PA, Lee P, Hung MC, Yung WK Expression of an altered epidermal growth factor receptor by human glioblastoma cells Cancer Res 48: 5433–5439, 1988

    PubMed  CAS  Google Scholar 

  73. Maxwell M, Naber SP, Wolfe HJ, Hedley-Whyte ET, Galanopoulos T, Neville-Golden J, Antoniades HN Expression of angiogenic growth factor genes in primary human astrocytomas may contribute to their growth and progression Cancer Res 51: 1345–1351, 1991

    PubMed  CAS  Google Scholar 

  74. Feldkamp MM, Lau N, Rak J, Kerbel RS, Guha A Normoxic and hypoxic regulation of vascular endothelial growth factor (VEGF) by astrocytoma cells is mediated by Ras Int J Cancer 81: 118–124, 1999

    Article  PubMed  CAS  Google Scholar 

  75. Platten M, Wick W, Weller M: Malignant glioma biology: role for TGF-beta in growth, motility, angiogenesis, and immune escape Microsc Res Tech 52: 401–410, 2001

    Article  PubMed  CAS  Google Scholar 

  76. Yamada N, Kato M, Yamashita H, Nister M, Miyazono K, Heldin CH, Funa K Enhanced expression of transforming growth factor-beta and its type-I and type-II receptors in human glioblastoma Int J Cancer 62: 386–392, 1995

    PubMed  CAS  Google Scholar 

  77. Rich JN, Zhang M, Datto MB, Bigner DD, Wang XF Transforming growth factor-beta-mediated p15(INK4B) induction and growth inhibition in astrocytes is SMAD3-dependent and a pathway prominently altered in human glioma cell lines J Biol Chem 274: 35053–35058, 1999

    Article  PubMed  CAS  Google Scholar 

  78. Jen J, Harper JW, Bigner SH, Bigner DD, Papadopoulos N, Markowitz S, Willson JK, Kinzler KW, Vogelstein B Deletion of p15 and p16 genes in brain tumors Cancer Res 54: 6353–6358, 1994

    PubMed  CAS  Google Scholar 

  79. Frater-Schroder M, Muller G, Birchmeier W, Bohlen P Transforming growth factor-beta inhibits endothelial cell proliferationBiochem Biophys Res Commun 137: 295–302, 1986

    Article  PubMed  CAS  Google Scholar 

  80. Fajardo LF, Prionas SD, Kwan HH, Kowalski J, Allison AC Transforming growth factor beta 1 induces angiogenesis in vivo with a threshold pattern Lab Invest 74: 600–608, 1996

    PubMed  CAS  Google Scholar 

  81. Stiles JD, Ostrow PT, Balos LL, Greenberg SJ, Plunkett R, Grand W, Heffner RR Jr Correlation of endothelin-1 and transforming growth factor beta 1 with malignancy and vascularity in human gliomas J Neuropathol Exp Neurol 56: 435–439, 1997

    PubMed  CAS  Google Scholar 

  82. Breier G, Blum S, Peli J, Groot M, Wild C, Risau W, Reichmann E Transforming growth factor-beta and Ras regulate the VEGF/VEGF-receptor system during tumor angiogenesis Int J Cancer 97: 142–148, 2002

    Article  PubMed  CAS  Google Scholar 

  83. Hjelmeland MD, Hjelmeland AB, Sathornsumetee S, Reese ED, Herbstreith MH, Laping NJ, Friedman HS, Bigner DD, Wang XF, Rich JN SB-431542, a small molecule transforming growth factor-beta-receptor antagonist, inhibits human glioma cell line proliferation and motility Mol Cancer Ther 3: 737–745, 2004

    PubMed  CAS  Google Scholar 

  84. Helseth E, Unsgaard G, Dalen A, Vik R: The effects of type beta transforming growth factor on proliferation and epidermal growth factor receptor expression in a human glioblastoma cell line J Neurooncol 6: 269–276, 1988

    Article  PubMed  CAS  Google Scholar 

  85. Platten M, Wick W, Wild-Bode C, Aulwurm S, Dichgans J, Weller M Transforming growth factors beta 1 (TGF-beta(1)) and TGF-beta(2) promote glioma cell migration via up-regulation of alpha(ν)beta(3) integrin expression Biochem Biophys Res Commun 268: 607–611, 2000

    Article  PubMed  CAS  Google Scholar 

  86. Arrieta O, Garcia E, Guevara P, Garcia-Navarrete R, Ondarza R, Remba D, Sotelo J Hepatocyte growth factor is associated with poor prognosis of malignant gliomas and is a predictor for recurrence of meningioma Cancer 94: 3210–3218, 2002

    Article  PubMed  CAS  Google Scholar 

  87. Kunkel P, Muller S, Schirmacher P, Stavrou D, Fillbrandt R, Westphal M, Lamszus K Expression and localization of scatter factor/hepatocyte factor in human astrocytomas Neuro-oncol 3: 82–88, 2001

    Article  PubMed  CAS  Google Scholar 

  88. Schmidt NO, Westphal M, Hagel C, Ergun S, Stavrou D, Rosen EM, Lamszus K Levels of vascular endothelial growth factor, hepatocyte growth factor/scatter factor and basic fibroblast growth factor in human gliomas and their relation to angiogenesis Int J Cancer 84: 10–18, 1999

    Article  PubMed  CAS  Google Scholar 

  89. Abounader R, Lal B, Luddy C, Koe G, Davidson B, Rosen EM, Laterra J: In vivo targeting of SF/HGF and c-met expression via U1snRNA/ribozymes inhibits glioma growth and angiogenesis and promotes apoptosis FASEB J 6: 108–110, 2002

    Google Scholar 

  90. Brockmann MA, Papadimitriou A, Brandt M, Fillbrandt R, Westphal M, Lamszus K Inhibition of intracerebral glioblastoma growth by local treatment with the scatter factor/hepatocyte growth factor-antagonist NK4 Clin Cancer Res 9: 4578–4585, 2003

    PubMed  CAS  Google Scholar 

  91. Jedsadayanmata A, Chen CC, Kireeva ML, Lau LF, Lam SC Activation-dependent adhesion of human platelets to Cyr61 and Fisp12/mouse connective tissue growth factor is mediated through integrin α(11b)β(3) Biol Chem 274: 24321–24327, 1999

    Article  CAS  Google Scholar 

  92. Kireeva ML, Latinkic BV, Kolesnikova TV, Chen CC, Yang GP, Alber AS, Lau LF Cyr61 and Fisp12 are both ECM-associated signaling molecules: activities, metabolism and localization during development Exp Cell Res 233: 63–77, 1997

    Article  PubMed  CAS  Google Scholar 

  93. Babic AM, Kireeva ML, Kolesnikova TV, Lau LF CYR61, a product of a growth factor-inducible immediate early gene, promotes angiogenesis and tumor growth Proc Natl Acad Sci USA 95: 6355–6360, 1998

    Article  PubMed  CAS  Google Scholar 

  94. Shimo T, Nakanishi T, Nishida T, Asano M, Kanyama M, Kuboki T, Tamatani T, Tezuka K, Takemura M, Matsumura T, Takigawa M Connective tissue growth factor induces the proliferation, migration, and tube formation of vascular endothelial cells in vitro, and angiogenesis in vivo J Biochem 126: 137–145, 1999

    PubMed  CAS  Google Scholar 

  95. Leu SJ, Lam SC, Lau LF Pro-angiogenic activities of Cyr61(CCN1) mediated through integrins alphaνbeta3 and alpha6beta1 in human umbilical vein endothelial cells J Biol Chem 277: 46248–46255, 2002

    Article  PubMed  CAS  Google Scholar 

  96. Xie D, Yin D, Wang HJ, Liu GT, Elashoff R, Black K, Koeffler HP Levels of expression of CYR61 and CTGF are prognostic for tumor progression and survival of individuals with gliomas Clin Cancer Res 10: 2072–2081, 2004

    Article  PubMed  CAS  Google Scholar 

  97. Pan LH, Beppu T, Kurose A, Yamauchi K, Sugawara A, Susuki M, Ogawa A, Sawai T Neoplastic cells and proliferating endothelial cells express connective tissue growth factor (CTGF) in glioblastoma Neurol Res 24: 677–683, 2002

    Article  PubMed  CAS  Google Scholar 

  98. Hirano H, Lopes MB, Laws ER Jr, Asakura T, Goto M, Carpenter JE, Karns LR, VandenBerg SR Insulin-like growth factor-1 content and pattern of expression correlates with histopathologic grade in diffusely infiltrating astrocytomas Neuro-oncol 1: 109–119, 1999

    Article  PubMed  CAS  Google Scholar 

  99. Van Meir E, Sawamura Y, Diserens AC, Hamou MF, de Tribolet N Human glioblastoma cells release interleukin 6 in vivo and in vitro Cancer Res 50: 6683–6688, 1990

    PubMed  Google Scholar 

  100. Van Meir E, Ceska M, Effenberger F, Walz A, Grouzmann E, Desbaillets I, Frei K, Fontana A, de Tribolet N Interleukin-8 is produced in neoplastic and infectious diseases of the human central nervous system Cancer Res 52: 4297–4305, 1992

    PubMed  Google Scholar 

  101. Rolhion C, Penault-Llorca F, Kemeny JL, Lemaire JJ, Jullien C, Labit-Bouvier C, Finat-Duclos F, Verrelle P Interleukin-6 overexpression as a marker of malignancy in human gliomas J Neurosurg 94: 97–101, 2001

    PubMed  CAS  Google Scholar 

  102. Brat DJ, Bellail AC, Van Meir EG The role of interleukin-8 and its receptors in gliomagenesis and tumoral angiogenesis Neuro-oncol 7: 122–133, 2005

    Article  PubMed  CAS  Google Scholar 

  103. Choi C, Gillespie GY, Van Wagoner NJ, Benveniste EN Fas engagement increases expression of interleukin-6 in human gliomas cells J Neurooncol 56: 13–19, 2002

    Article  PubMed  Google Scholar 

  104. Koch AE, Polverini PJ, Kunkel SL, Harlow LA, DiPietro LA,Elner VM, Elner SG, Strieter RM Interleukin-8 as a macrophage-derived mediator of angiogenesis Science 258:1798–1801, 1992

    PubMed  CAS  Google Scholar 

  105. Hu DE, Hori Y, Fan TP Interleukin-8 stimulates angiogenesis in rats Inflammation 17: 135–143, 1993

    Article  PubMed  CAS  Google Scholar 

  106. Desbaillets I, Diserens AC, Tribolet N, Hamon MF, Van Meir EG Upregulation of Interleukin-8 by oxygen-deprived cells in glioblastoma suggests a role in leukocyte activation, chemotaxis and angiogenesis J Exp Med 186:1201–1212, 1997

    Article  PubMed  CAS  Google Scholar 

  107. Wakabayashi Y, Shono T, Isono M, Hori S, Matsushima K, Ono M, Kuwano M Dual pathways of tubular morphogenesis of vascular endothelial cells by human gliomas cells: vascular endothelial growth factor/ basic fibroblast growth factor and interleukin-8.Jpn J Cancer Res 86: 1189–1197, 1995

    CAS  Google Scholar 

  108. Desbaillets I, Diserens AC, de Tribolet N, Hamon MF, Van Meir EG Regulation of interleukin-8 expression by reduced oxygen pressure in human glioblastoma Oncogene 18: 1447–1456, 1999

    Article  PubMed  CAS  Google Scholar 

  109. Fajardo LF, Kwan HH, Kowalski J, Prionas SD, Allison AC Dual role of tumor necrosis factor-alpha in angiogenesis Am J Pathol 140: 539–544, 1992

    PubMed  CAS  Google Scholar 

  110. Maruno M, Kovach JS, Kelly PJ, Yanagihara T Distribution of endogenous tumor necrosis factor alpha in gliomas J Clin Pathol 50: 559–562, 1997

    PubMed  CAS  Google Scholar 

  111. Roessler K, Suchanek G, Breitschopf H, Kitz K, Matula C, Lassmann H, Koos WT Detection of tumor necrosis factor-alpha protein and messenger RNA in human glial brain tumors: comparison of immunohistochemistry with in situ hybridization using molecular probes J Neurosurg 83: 291–297, 1995

    Article  PubMed  CAS  Google Scholar 

  112. Slowik MR, De Luca LG, Fiers W, Prober JS Tumor necrosis factor activates human endothelial cells through the p55 tumor necrosis factor receptor but the p75 receptor contributes to activation at low tumor necrosis factor concentration Am J Pathol 143: 1724–1730, 1993

    PubMed  CAS  Google Scholar 

  113. Puduvalli VK, Sawaya R Antiangiogenesis-therapeutic strategies and clinical implications for brain tumors J Neurooncol 50: 189–200, 2000

    Article  PubMed  CAS  Google Scholar 

  114. Rao JS, Yamamoto M, Mohaman S, Gokaslan ZL, Fuller GN, Stetler-Stevenson WG, Rao VH, Liotta LA, Nicolson GL, Sawaya RE Expression and localization of 92kDa type IV collagenase/gelatinase B (MMP-9) in human gliomas Clin Exp Metastasis 14: 12–18, 1996

    Article  PubMed  CAS  Google Scholar 

  115. Forsyth PA, Wong H, Laing TD, Rewcastle NB, Morris DG, Muzik H, Leco KJ, Johnston RN, Brasher PM, Sutherland G, Edwards DR Gelatinase-A (MMP-2), gelatinase-B (MMP-9) and membrane type matrix metalloproteinase-1 (MT1-MMP) are involved in different aspects of the pathophysiology of malignant gliomas Br J Cancer 79:1828–1835, 1999

    Article  PubMed  CAS  Google Scholar 

  116. Binder DK, Berger MS Proteases and the biology of glioma invasion J Neurooncol 56: 2002

  117. Yu Q, Stamenkovic I Cell surface-localized matrix metalloproteinase-9 proteolytically activates TGF-beta and promotes tumor invasion and angiogenesis Genes Dev 14: 163–176, 2000

    PubMed  Google Scholar 

  118. Bergers G, Brekken R, McMahon G, Vu TH, Itoh T, Tamaki K, Tanzawa K, Thorpe P, Itohara S, Werb Z, Hanahan D Matrix metalloproteinase-9 triggers the angiogenic switch during carcinogenesis Nat Cell Biol 2: 737–744, 2000

    Article  PubMed  CAS  Google Scholar 

  119. Rooprai HK, Rucklidge GJ, Panou C, Pilkington GJ The effects of exogenous growth factors on matrix metalloproteinase secretion by human brain tumour cells Br J Cancer 82: 52–55, 2000

    Article  PubMed  CAS  Google Scholar 

  120. Wick W, Platten M, Weller M Glioma cell invasion: regulation of metalloproteinase activity by TGF-beta J Neurooncol 53: 177–185, 2001

    Article  PubMed  CAS  Google Scholar 

  121. Lamoreaux WJ, Fitzgerald MEC, Reiner A, Hasty KA, Charles ST Vascular endothelial growth factor increases release of gelatinase a and decreases release of tissue inhibitor of metalloproteinases by microvascular endothelial cells in vitro Microvasc Res 55: 29–42, 1998

    Article  PubMed  CAS  Google Scholar 

  122. Wagner S, Fueller T, Hummel V, Rieckmann P, Tonn JC Influence of VEGF-R2 inhibition on MMP secretion and motility of microvascular human cerebral endothelial cells (HCEC) J Neurooncol 62: 221–231, 2003

    Article  PubMed  Google Scholar 

  123. Jadhav U, Chigurupati S, Lakka SS, Mohanam S Inhibition of matrix metalloproteinase-9 reduces in vitro invasion and angiogenesis in human microvascular endothelial cells Int J Oncol 25: 1407–1414, 2004

    PubMed  CAS  Google Scholar 

  124. Nakada M, Nakamura H, Ikeda E, Fujimoto N, Yamashita J, Sato H, Seiki M, Okada Y Expression and tissue localization of membrane-type 1,2 and 3 matrix metalloproteinases in human astrocytic tumors Am J Pathol 154: 417–428, 1998

    Google Scholar 

  125. Hotary K, Allen E, Punturieri A, Yana I, Weiss SJ Regulation of cell invasion and morphogenesis in a three-dimensional type I collagen matrix by membrane-type matrix metalloproteinases 1, 2 and 3 J Cell Biol 149: 1309–1323, 2000

    Article  PubMed  CAS  Google Scholar 

  126. Hiraoka N, Allen E, Apel IJ, Gyetko MR, Weiss SJ Matrix metalloproteinases regulate neovascularization by acting as pericellular fibrinolysins Cell 95: 365–377, 1998

    Article  PubMed  CAS  Google Scholar 

  127. Deryugina EI, Ratnikov B, Monosov E, Postnova T, DiScipio R, Smith JW, Strongin A MT1-MMP initiates activation of MMP-2 and integrin ανβ3 promotes maturation of MMP-2 in breast carcinoma cells Exp Cell Res 263: 209–223, 2001

    Article  PubMed  CAS  Google Scholar 

  128. Deryngina EI, Soroceanu L, Strongin AY Up-regulation of vascular endothelial growth factor by membrane-type 1 matrix metalloproteinase stimulates human glioma xenograft growth and angiogenesis Cancer Res 62: 580–588, 2002

    PubMed  Google Scholar 

  129. Yamamoto M, Sawaya R, Mohanam S, Bindal AK, Brunner JM, Oka K, Rao VH, Tomonaga M, Nicolson GL, Rao JS Expression and localization of urokinase-type plasminogen activator in human astrocytomas in vivo Cancer Res 54: 3656–3661, 1994

    PubMed  CAS  Google Scholar 

  130. Yamamoto M, Sawaya R, Mohanam S, Rao VH, Brunner JM, Nicolson GL, Rao JS Expression and localization of urokinase-type plasminogen activator receptor in human gliomas Cancer Res 54: 5016–5020, 1994

    PubMed  CAS  Google Scholar 

  131. Dumler I, Weis A, Mayboroda OA, Maasch C, Jerke U, Haller H, Gulba DC The Jak/Stat pathway and urokinase receptor signaling in human aortic vascular smooth muscle cells J Biol Chem 273: 315–321, 1998

    Article  PubMed  CAS  Google Scholar 

  132. Nguyen DH, Hussaini IM, Gonias SL Binding of urokinase-type plasminogen activator to its receptor in MCF-7 cells activates extracellular signal-regulated kinase 1 and 2 which is required for increased cellular motility J Biol Chem 273: 8502–8507, 1998

    Article  PubMed  CAS  Google Scholar 

  133. Mazzieri R, Masiero L, Zanetta L, Monea S, Onisto M, Garbisa S, Mignatti P Control of type IV collagenase activity by components of the urokinase-plasmin system: a regulatory mechanism with cell-bound reactants EMBO J 16: 2319–2332, 1997

    Article  PubMed  CAS  Google Scholar 

  134. Lakka SS, Gondi CS, Dinh DH, Olivero WC, Gujrati M, Rao VH, Sioka C, Rao JS Specific interference of urokinase-type plasminogen activator receptor and matrix metalloproteinase-9 gene expression induced by double-stranded RNA results in decreased invasion, tumor growth and angiogenesis in gliomas J Biol Chem 280: 21882–21892, 2005

    Article  PubMed  CAS  Google Scholar 

  135. Stromblad S, Cheresh DA Integrins, angiogenesis and vascular cell survival Chem Biol 3:881–885, 1996

    Article  PubMed  CAS  Google Scholar 

  136. Bello L, Francolini M, Marthyn P, Zhang J, Carroll RS, Nikas DC, Strasser JF, Villani R, Cheresh DA, Black PM Alpha(ν)beta3 and alpha(ν)beta5 integrin expression in glioma periphery Neurosurgery 49: 380–309, 2001

    Article  PubMed  CAS  Google Scholar 

  137. Brooks PC, Stromblad S, Sanders LC, von Schalscha TL, Aimes RT, Stetler-Stevenson WG, Quigley JP, Cheresh DA Localization of matrix metalloproteinase MMP-2 to the surface of invasive cells by interaction with integrin alphaνbeta3 Cell 85:683–693, 1996

    Article  PubMed  CAS  Google Scholar 

  138. Bogler O, Mikkelsen T Angiogenesis and apoptosis in glioma. Two arenas for promising new therapies J Cell Biochem 96: 16–24, 2005

    Article  PubMed  CAS  Google Scholar 

  139. Horton MA The alphaνbeta3 integrin ‘vitronectin receptor’ Int J Biochem Cell Biol 29: 721–725, 1997

    Article  PubMed  CAS  Google Scholar 

  140. Stupack DG, Cheresh DA Get a ligand, get a life: Integrins, signaling and cell survival J Cell Sci 115: 3729–3738, 2002

    Article  PubMed  CAS  Google Scholar 

  141. Friedlander M, Brooks PC, Shaffer RW, Kincaid CM, Varner JA, Cheresh DA Definition of two angiogenic pathways by distinct alpha ν integrins Science 270: 1500–1502, 1995

    PubMed  CAS  Google Scholar 

  142. Brooks PC, Montgomery AM, Rosenfeld M, Reisfeld RA, Hu T, Klier G, Cheresh DA Integrin alpha ν beta 3 antagonists promote tumor regression by inducing apoptosis of angiogenic blood vessels Cell 79: 1157–1164, 1994

    Article  PubMed  CAS  Google Scholar 

  143. Brooks PC, Clark RA, Cheresh DA: Requirement of vascular integrin alpha ν beta 3 for angiogenesis Science 264: 569–571, 1994

    PubMed  CAS  Google Scholar 

  144. Mikkelsen T, Yan PS, Ho KL, Sameni M, Sloane BF, Rosenblum ML Immunolocalization of cathepsin B in human glioma: implications for tumor invasion and angiogenesis J Neurosurg 83: 285–290, 1995

    PubMed  CAS  Google Scholar 

  145. Wang M, Tang J, Liu S, Yoshida D, Teramoto A Expression of cathepsin B and microvascular density increases with higher grade of astrocytomas J Neurooncol 71:3–7, 2005

    Article  PubMed  CAS  Google Scholar 

  146. Murphy G, Atkinson S, Ward R, Gavrilovic J, Reynolds JJ The role of plasminogen activators in the regulation of connective tissue metalloproteinases Ann N Y Acad Sci 667: 1–12, 1992

    PubMed  CAS  Google Scholar 

  147. Guo M, Mathieu PA, Linebaugh B, Sloane BF, Reiners JJ Jr Phorbol ester activation of a proteolytic cascade capable of activating transforming growth factor-betaL a process initiated by exocytosis of cathepsin B J Biol Chem 277: 14829–14837, 2002

    Article  PubMed  CAS  Google Scholar 

  148. Kostoulas G, Lang A, Nagase H, Baici A Stimulation of angiogenesis through cathepsin B inactivation of the tissue inhibitors of matrix metalloproteinases FEBS Lett 455: 286–290, 1999

    Article  PubMed  CAS  Google Scholar 

  149. Yanamandra N, Gumidyala KV, Waldron KG, Gujrati M, Olivero WC, Dinh DH, Rao JS, Mohanam S Blockade of cathepsin B expression in human glioblastoma cells is associated with suppression of angiogenesis Oncogene 23: 2224–2230, 2004

    Article  PubMed  CAS  Google Scholar 

  150. Gondi CS, Lakka SS, Dinh DH, Olivero WC, Gujrati M, Rao JS RNA i-mediated inhibition of cathepsin B and uPAR leads to decreased cell invasion, angiogenesis and tumor growth in gliomas Oncogene 23: 8486–8496, 2004

    Article  PubMed  CAS  Google Scholar 

  151. Lakka SS, Gondi CS, Yanamandra N, Olivero WC, Dinh DH, Gujrati M, Rao JS Inhibition of cathepsin B and MMP-9 gene expression in glioblastoma cell line via RNA interference reduces tumor cell invasion, tumor growth and angiogenesis Oncogene 23: 4681–4689, 2004

    Article  PubMed  CAS  Google Scholar 

  152. Mai J, Sameni M, Mikkelsen T, Sloane BF, Degradation of extracellular matrix protein tenascin-C by cathepsin B: an interaction involved in the progression of gliomas Biol Chem 383: 1407–1413, 2002

    Article  PubMed  CAS  Google Scholar 

  153. Jones FS, Jones PL The tenascin family of ECM glycoproteins: structure, function and regulation during embryonic development and tissue remodeling Dev Dyn 218: 235–259, 2000

    Article  PubMed  CAS  Google Scholar 

  154. Chung CY, Murphy-Ullrich JE, Erickson HP Mitogenesis, cell migration and loss of focal adhesions induced by tenascin-C interacting with its cell surface receptor, annexin II Mol Biol Cell 7: 883–892, 1996

    PubMed  CAS  Google Scholar 

  155. Zagzag D, Friedlander DR, Miller DC, Dosik J, Cangiarella J, Kostianovsky M, Cohen H, Grumet M, Greco MA Tenascin expression in astrocytomas correlates with angiogenesis Cancer Res 55: 907–914, 1995

    PubMed  CAS  Google Scholar 

  156. Zagzag D, Friedlander DR, Dosik J, Chikramane S, Chan W, Greco MA, Allen JC, Dorovini-Zis K, Grumet M Tenascin-C expression by angiogenic vessels in human astrocytomas and by human brain endothelial cells in vitro Cancer Res 56: 182–189, 1996

    PubMed  CAS  Google Scholar 

  157. Zagzag D, Shiff B, Jallo GI, Greco MA, Blanco C, Cohen H, Hukin J, Allen JC, Friedlander DR Tenascin-C promotes microvascular cell migration and phosphorylation of Focal Adhesion Kinase Cancer Res 62: 2660–2668, 2002

    PubMed  CAS  Google Scholar 

  158. Meiners S, Marone M, Rittenhouse JL, Geller HM Regulation of astrocytic tenascin by basic fibroblast growth factor Dev Biol 160: 480–493, 1993

    Article  PubMed  CAS  Google Scholar 

  159. Pearson CA, Pearson D, Shibahara S, Hofsteenge J, Chiquet-Ehrismann R Tenascin: cDNA cloning and induction by TGF-beta EMBO J 7:2977–2982, 1998

    Google Scholar 

  160. Sriramarao P, Mendler M, Bourdon MA Endothelial cell attachment and spreading on human tenascin is mediated by 2 beta 1 and ν beta 3 integrins J Cell Sci 105: 1001–1012, 1993

    PubMed  CAS  Google Scholar 

  161. Haskell H, Natarajan M, Hecker TP, Ding Q, Stewart J Jr, Grammer JR, Gladson CL Focal adhesion Kinase is expressed in the angiogenic blood vessels of malignant astrocytic tumors in vivo and promotes capillary tube formation of brain microvascular endothelial cells Clin Cancer Res 9: 2157–2165, 2003

    PubMed  CAS  Google Scholar 

  162. Burridge K, Turner CE, Romer LH Tyrosine phosphorylation of paxillin and pp 125FAK accompanies cell adhesion to extracellular matrix: a role in cytoskeletal assembly J Cell Biol 119: 893–903, 1992

    Article  PubMed  CAS  Google Scholar 

  163. Zheng PS, Wen J, Ang LC, Sheng W, Viloria-Petit A, Wang Y, Wu Y, Kerbel RS, Yang BB Versican/PG-M G3 domain promotes tumor growth and angiogenesis FASEB J 18: 754–756, 2004

    PubMed  CAS  Google Scholar 

  164. Chekenya M, Rooprai HK, Davies D, Levine JM, Butt AM, Pilkington GJ The NG2 chondroitin sulphate proteoglycan: role in malignant progression of human brain tumors Int J Dev Neurosci 17: 421–435, 1999

    Article  PubMed  CAS  Google Scholar 

  165. Chekenya M, Hjelstuen M, Enger PO, Thorsen F, Jacob AL, Probst B, Haraldseth O, Pilkington G, Butt A, Levine JM, Bjerkvig R NG2 proteoglycan promotes angiogenesis-dependent tumor growth in CNS by sequestering angiostatin FASEB J 16: 586–588, 2002

    PubMed  CAS  Google Scholar 

  166. Le Y, Hu J, Gong W, Shen W, Li B, Dunlop NM, Halverson DO, Blair DG, Wang JM Expression of functional formyl peptide receptors by human astrocytoma cell lines J Neuroimmunol 111: 102–108, 2000

    Article  PubMed  CAS  Google Scholar 

  167. Zhou Y, Bian X, Le Y, Gong W, Hu J, Zhang X, Wang L, Iribarren P, Salcedo R, Howard OM, Farrar W, Wang JM Formylpeptide receptor FPR and the rapid growth of malignant human gliomas J Natl Cancer Inst 97: 823–35, 2005

    Article  PubMed  CAS  Google Scholar 

  168. Bromberg JF, Wrzeszczynska MH, Devgan G, Zhao Y, Pestell RG, Albanese C, Darnell JE Jr Stat3 as an oncogene Cell 98: 295–303, 1999

    Article  PubMed  CAS  Google Scholar 

  169. Salmaggi A, Gelati M, Pollo B, Frigerio S, Eoli M, Silvani A, Broggi G, Ciusani E, Croci D, Boiardi A, De Rossi M CXCL12 in malignant glial tumors: a possible role in angiogenesis and cross-talk between endothelial and tumoral cells J Neurooncol 67: 305–317, 2004

    Article  PubMed  Google Scholar 

  170. Yao Y, Kubota T, Sato K, Kitai R Macrophage infiltration-associated thymidine phosphorylase expression correlates with increased microvessel density and poor prognosis in astrocytic tumors Clin Cancer Res 7: 4021–4026, 2001

    PubMed  CAS  Google Scholar 

  171. Hirano H, Tanioka K, Yokoyama S, Akiyama S, Kuratsu J Angiogenic effect of thymidine phosphorylase on macrophages in glioblastoma multiforme J Neurosurg 95: 89–95, 2001

    Article  PubMed  CAS  Google Scholar 

  172. Vajkoczy P, Blum S, Lamparter M, Mailhammer R, Erber R, Engelhardt B, Vestweber D, Hatzopoulos AK Multistep nature of microvascular recruitment of ex vivo-expanded embryonic endothelial progenitor cells during tumor angiogenesis J Exp Med 197: 1755–1765, 2003

    Article  PubMed  CAS  Google Scholar 

  173. Khodarev NN, Yu J, Labay E, Darga T, Brown CK, Mauceri HJ, Yassari R, Gupta N, Weichselbaum RR Tumor-endothelium interactions in co-culture: coordinated changes of gene expression profiles and phenotypic properties of endothelial cells J Cell Sci 116: 1013–1022, 2003

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Neurosurgical Institute, University of Ioannina Medical School, Ioannina, Greece

    O. Kargiotis & A.P. Kyritsis

  2. Division of Cancer Biology, Department of Biomedical and Therapeutic Sciences, University of Illinois College of Medicine at Peoria, Peoria, IL, USA

    J.S. Rao

  3. Department of Neurology, University of Ioannina Medical School, Ioannina, Greece

    A.P. Kyritsis

  4. Department of Neurology, University of Ioannina Medical School, 1 Panepistimioupoli, GR-451 10, Ioannina, Greece

    A.P. Kyritsis

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Kargiotis, O., Rao, J. & Kyritsis, A. Mechanisms of angiogenesis in gliomas. J Neurooncol 78, 281–293 (2006). https://doi.org/10.1007/s11060-005-9097-6

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