Vascular morphology and angiogenesis in glial tumors

https://doi.org/10.1016/S0940-2993(11)80292-7Get rights and content

Summary

Intracranial tumor classification is paralleled by a grading system that empirically compares tumor entities with ‘progression stages” of supratentorial gliomas of the adult. This grading system is an integral part of the WHO classification. Glioma progression has originally been defined by descriptive morphology. In this respect, morphological key features of high-grade gliomas (WHO grades III and IV) are microvascular proliferation and the formation of tumor necroses. Glioma progression is now more accurately defined on the molecular genetic level by a stepwise accumulation of oncogene activation and/or tumor suppressor gene inactivation.

Angiogenesis occures during development and progression of glial tumors. Pathological vessels are a hallmark of malignant glioma and it has therefore been suggested that malignant glioma cells are able to induce neovascularization. Despite the exuberant neovascularisation, however, vascular supply may not be sufficient for tumor areas with high cell proliferation, and necroses may develop. Malignant transformation of blood vessel itself is a rare event but may be the underlying mechanism of gliosarcoma development.

The recently purified vascular endothelial growth factor (VEGF) is at present the only mitogen known to selectively act on endothelial cells. Growing evidence suggests that VEGF is the key regulator of developmental and pathological angiogenesis. In vivo, VEGF mRNA is upregulated in a subpopulation of malignant glioma cells adjacent to necroses. Since VEGF is hypoxia-inducible, hypoxia may be an important regulator of VEGF mRNA expression and tumor angiogenesis in vivo. Two tyrosine kinase receptors for VEGF are expressed in vessels which invade the tumor, suggesting that tumor angiogenesis is regulated by a paracrine mechanism.

The analysis of mechanisms which regulate tumor and/or hypoxia induced angiogenesis can be of importance for the biology, diagnosis and treatment of both ischemic and neoplastic diseases.

References (62)

  • J Folkman

    What is the evidence that tumor growth is angiogenesis dependent?

    J Natl Cancer Inst

    (1990)
  • J Folkman

    Tumor angiogenesis

  • Folkman J. Antiangiogenesis. In: Devita VT, Hellmann S, Rosenberg SA (Eds.): Biological therapy of cancer. Lipincott...
  • J Folkman et al.

    Angiogenic factors

    Science

    (1987)
  • IM Germano et al.

    Correlation of histopathological features and proliferative potential of gliomas

    J Neurosurg

    (1989)
  • F Giangaspero et al.

    Growth fraction in human brain tumors defined by the monoclonal antibody Ki-67

    Acta Neuropathol

    (1987)
  • CK Goldman et al.

    Epidermal growth factor stimulates vascular endothelial growth factor production by human malignant glioma cells: a model of glioblastoma multiforme pathophysiology

    Mol Biol Cell

    (1993)
  • SF Haddah et al.

    Vascular smooth muscle hyperplasia underlies the formation of glomeruloid vascular structures of glioblastoma multiforme

    J Neuropath Exp Neuropathol

    (1992)
  • SF Haddah et al.

    Smooth muscle cells can compromise the sarcomatous component of gliosarcomas

    J Neuropath Exp Neuropathol

    (1992)
  • J Hardmann

    The angioarchitecture of the glioma

    Brain

    (1940)
  • M Hermansson et al.

    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

    (1988)
  • T Hoshino et al.

    Prognostic implications of the bromodeoxyuridine labeling index of human gliomas

    J Neurosurg

    (1989)
  • CD James et al.

    Clonal genomic alterations in glioma malignancy stages

    Cancer Res

    (1988)
  • JW Kernohan et al.

    A simplified classification of the gliomas. Symposium on a new simplified concept of gliomas

    Proc Staff Meet Mayo Clin

    (1949)
  • P Kleihues et al.

    Histological Typing of Tumours of the Central Nervous System. World Health Organization, International Histological Classification of Tumours

    (1993)
  • P Kleihues et al.

    The New WHO Classification of Brain Tumours

    Brain Pathology

    (1993)
  • K Kunisho et al.

    Immunohistochemical demonstration of DNA polymerase a in human brain-tumor cells

    J Neurosurg

    (1990)
  • TA Libermann et al.

    Amplification, enhanced expression and possible rearrangement of the EGF receptor in primary human brain tumors of glial origin

    Nature

    (1985)
  • DM Long

    Capillary ultrastructure and the blood-brain barrier in human malignant brain tumors

    J Neurosurg

    (1970)
  • M Maxwell et al.

    Expression of angiogenic growth factor genes in primary human astrocytomas may contribute to their growth and progression

    Cancer Res

    (1991)
  • Cited by (108)

    • Precise gliomas therapy: Hypoxia-activated prodrugs sensitized by nano-photosensitizers

      2022, Biomaterials
      Citation Excerpt :

      Glioma, particularly glioblastoma multiforme (GBM, grade IV, the most malignant [26]), is one of the most incurable tumors in primary central nervous system (CNS) due to the grave growth infiltration, extremely fast-spreading speed and grievously high recurrence rate [27–30]. Compared with other tumors, gliomas are characterized by hypoxia (< 10 mmHg) [31], which is imputed to the vascular folding caused by over-recruitment or proliferation of endothelial cells and lack of pericyte coating [32,33]. Consequently, HAPs possess a great therapy prospect in gliomas.

    • Evaluation of anti-angiogenic agent F16 for targeting glioblastoma xenograft tumors

      2022, Cancer Genetics
      Citation Excerpt :

      Various preclinical studies have indicated that the growth ability of GBM critically depends on the generation of tumor-associated hyper-permeable blood vessels [1,4] that are characterized by a dense network with abnormally increased vessel diameter and thickness of basement membranes. This aberrant tumor vasculature is believed to enhance GBM growth and facilitate tumor metastasis that is contributing to treatment failure [5,6]. Therefore, antagonizing tumor vascular has been used as a strategy for brain tumor treatment, particularly for the GBM.

    • Functional magnetic resonance imaging

      2022, Handbook of Neuro-Oncology Neuroimaging
    • Imaging of glioblastoma recurrence

      2021, New Targeting in the Reversal of Resistant Glioblastomas
    View all citing articles on Scopus
    View full text