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The Relationship Between Genetic Aberrations as Detected by Comparative Genomic Hybridization and Vascularization in Glioblastoma Xenografts

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Abstract

Angiogenesis is of vital importance for the growth of solid tumors and constitutes a target for anti-cancer therapy. Glioblastomas (GBMs) are histologically characterized by striking microvascular proliferation. The identification of the mechanism of angiogenesis is of major importance for the further development of anti-angiogenic therapy. Tumor angiogenesis might be the result of a combination of local tissue conditions (especially hypoxia) and specific genetic alterations acquired during oncogenesis. In order to investigate the relationship between genetic aberrations and tumor angiogenesis in GBM xenograft lines, the genetic alterations were examined by Comparative Genomic Hybridization (CGH). Two vascular phenotypes of GBM xenografts could be identified: a well vascularized and a poorly vascularized type. In this model, the poorly vascularized type had a larger number of genetic alterations. However, there was no unequivocal correlation between angiogenesis, growth rate and patterns of genetic alterations as detected by CGH.

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References

  1. Folkman J: Tumor angiogenesis: therapeutic implications. N Eng J Med 285: 1182–1186, 1971

    Google Scholar 

  2. Folkman J: Clinical applications of research on angiogenesis. N Eng J Med 333: 1757–1763, 1995

    Google Scholar 

  3. Mahaley MS, Mettlin C, Natarajan N, Laws ER, Peace BB: National survey of patterns of care for brain-tumor patients. J Neurosurg 71: 826–836, 1989

    PubMed  Google Scholar 

  4. Kleihues P, Burger PC, Scheithauer BW: The new WHO classification of brain tumors. Brain Pathol 3: 255–268, 1993

    PubMed  Google Scholar 

  5. Mastronardi L, Puzzilli F, Couldwell WT, Farah JO, Lunardi P: Tamoxifen and carboplatin combinational treatment of high-grade gliomas. J Neuro-Oncol 38: 59–68, 1998

    Google Scholar 

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

    PubMed  Google Scholar 

  7. Lund EL, Spang-Thomsen M, Skovgaard-Poulsen H, Kristjansen PEG: Tumor angiogenesis – a new therapeutic target in gliomas. Acta Neurol Scand 97: 52–62, 1998

    PubMed  Google Scholar 

  8. 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

    PubMed  Google Scholar 

  9. Shweiki D, Itin A, Soffer D, et al.: Vascular endothelial growth factor induced by hypoxia may mediate hypoxiainitiated angiogenesis. Nature 359: 843–845, 1992

    PubMed  Google Scholar 

  10. Plate KH, Breier G, Millauer B, Ullrich A, Risau W: Up-regulation of vascular endothelial growth factor and its cognate receptors in a rat glioma model of tumor angiogenesis. Cancer Res 53: 5822–5827, 1993

    PubMed  Google Scholar 

  11. Hanahan D, Folkman J: Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell 86: 353–364, 1996

    PubMed  Google Scholar 

  12. Kerbel RS, Viloria-Petit A, Okada F, Rak J: Establishing a link between oncogenes and tumor angiogenesis. Mol Med 4: 286–295, 1998

    PubMed  Google Scholar 

  13. Rak J, Filmus J, Finkenzeller G, Grugel S, Marme D, Kerbel RS: Oncogenes as inducers of tumor angiogenesis. Cancer Met Rev 14: 263–277, 1995

    Google Scholar 

  14. Takaki S, Kuratsu J, Mihara Y, Yamada M, Ushio Y: Endothelial cell chemotactic factor derived from human glioma cell lines. J Neurosurg 76: 822–829, 1992

    PubMed  Google Scholar 

  15. Laterra J, Indurti RR, Goldstein GW: Regulation of in vitro glia-induced microvessel morphogenesis by urokinase. J Cell Physiol 158: 317–324, 1994

    PubMed  Google Scholar 

  16. Louis DN, Gusella JF: A tiger behind many doors: multiple pathways to malignant glioma. Trends Genet 11: 412–415, 1995

    PubMed  Google Scholar 

  17. Wesseling P, van der Laak AWM, Link M, Teepen H, Ruiter DJ: Quantatitive analysis of microvascular changes in diffuse astrocytic neoplasms with increasing grade of malignancy. Hum Pathol 29: 352–358, 1998

    PubMed  Google Scholar 

  18. Bernsen HJJA, Rijken PFJW, Oostendorp T, van der Kogel AJ: Vascularity and perfusion of human glioma xenografted in the athymic nude mouse. Br J Cancer 71: 721–726, 1995

    PubMed  Google Scholar 

  19. Jeuken JWM, Sprenger SHE, Wesseling P, Bernsen HJJA, Suijkerbuijk RF, Roelofs F, Macville MVE, Gilhuis HJ, van Overbeeke JJ, Boerman RH: Genetic reflection of glioblastoma biopsy material in xenografts: Characterization of 11 glioblastoma xenograft lines by comparative genomic hybridization. J Neurosurg 92: 652–658, 2000

    PubMed  Google Scholar 

  20. Arteel GE, Thurman RG, Yates JM, Raleigh JA: Evidence that hypoxia markers detect oxygen gradients in liver: pimonidazole and retrograde perfusion of rat liver. Br J Cancer 72: 889–895, 1995

    PubMed  Google Scholar 

  21. Raleigh JA, Calkins-Adams DP, Rinker LH, Ballenger CA, Weissler MC, Fowler WC, Novotny DB, Varia MA: Hypoxia and vascular endothelial growth factor expression in human squamous cell carcinomas using pimonidazole as hypoxic marker. Cancer Res 58: 3765–3768, 1998

    PubMed  Google Scholar 

  22. Westphal JR, van't Hullenaar RGM, van der Laak JAWM, Cornelissen IMHA, Schalkwijk LJM, van Muijen GNP, Wesseling P, de Wilde PCM, Ruiter DJ, de Waal RMW: Vascular density in melanoma xenografts correlates with vascular permeability factor expression but not with metastatic potential. Br J Cancer 76: 561–570, 1997

    PubMed  Google Scholar 

  23. Rijken PFJW, Bernsen HJJA, van der Kogel AJ: Application of an image analysis system to the quantitation of tumor perfusion and vascularity in human glioma xenografts. Microvasc Res 50: 141–153, 1995

    PubMed  Google Scholar 

  24. Jeuken JWM, Sprenger SHE, Wesseling P, MacVille MVE, von Deimling A, Teepen HLJM, van Overbeeke JJ, Boerman RH: Identification of subgroups of high grade oligodendroglial tumors by comparative genomic hybridization. J Neuropathol Exp Neurol 58: 606–612, 1999

    PubMed  Google Scholar 

  25. Mohapatra G, Bollen AW, Kim DH, Lamborn K, Moore DH, Prados M, Feuerstein BG: Genetic analysis of glioblastoma multiforme provides evidence for subgroups within the grade. Genes Chromosomes Cancer 21: 195–206, 1998

    PubMed  Google Scholar 

  26. Schroeck E, Thiel G, Lozanova T, et al.: Comparative genomic hybridization of human malignant gliomas reveals multiple amplification sites and non-random chromosomal gains and losses. Am J Pathol 144: 1203–1218, 1994

    PubMed  Google Scholar 

  27. Gulledge CJ, Dewhirst MW: Tumour oxygenation: a matter of supply and demand. Anticancer Res 16: 741–750, 1996

    PubMed  Google Scholar 

  28. Bentz M, Plesch A, Stilgenbauer S, Dohner H, Lichtcr P: Minimal sizes of deletions detected by comparative genomic hybridization. Genes Chromosomes Cancer 21: 172–175, 1998

    PubMed  Google Scholar 

  29. Kallioniemi A, Kallioniemi O-P, Piper J, Tanner M, Stokke T, Chen L, Smith HS, Pinkel D, Gray JW, Waldman FM: Detection and mapping of amplified DNA sequences in breast cancer by comparative genomic hybridization. Proc Natl Acad Sci USA 91: 2156–2160, 1994

    PubMed  Google Scholar 

  30. Jung V, Romeike BF, Henn W, Feiden W, Moringlane JR, Zang KD, Urbschat S: Evidence of focal genetic microheterogeneity in glioblastoma multiforme by area-specific CGH on microdissected tumor cells. J Neuropathol Exp Neurol 58: 993–999, 1999

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Neurology, University Medical Hospital Center St Radboud, Nijmegen

    H. Jacobus Gilhuis & Pieter Wesseling

  2. Department of Radiotherapy, University Medical Hospital Center St Radboud, Nijmegen

    Hans J.J.A. Bernsen

  3. Department of Neurology, Canisius Wilhelmina Hospital, Nijmegen

    Hans J.J.A. Bernsen

  4. Department of Neurosurgery, University Medical Hospital Center St Radboud, Nijmegen

    Judith W.M. Jeuken

  5. Department of Pathology, University Medical Hospital Center St Radboud, Nijmegen

    Judith W.M. Jeuken, Pieter Wesseling, Sandra H.E. Sprenger & Harold M.J. Kerstens

  6. Department of Cytochemistry and Cytometry, University of Leiden, Leiden

    Joop Wiegant

  7. Department of Neurology, Rijnstaete Hospital, Arnhem, The Netherlands

    Rudolf H. Boerman

Authors
  1. H. Jacobus Gilhuis
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  2. Hans J.J.A. Bernsen
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  3. Judith W.M. Jeuken
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  4. Pieter Wesseling
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  5. Sandra H.E. Sprenger
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  6. Harold M.J. Kerstens
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  7. Joop Wiegant
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  8. Rudolf H. Boerman
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Gilhuis, H.J., Bernsen, H.J., Jeuken, J.W. et al. The Relationship Between Genetic Aberrations as Detected by Comparative Genomic Hybridization and Vascularization in Glioblastoma Xenografts. J Neurooncol 51, 121–127 (2001). https://doi.org/10.1023/A:1010675831154

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  • DOI: https://doi.org/10.1023/A:1010675831154

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