Abstract
The growth of solid tumors is highly dependent on vascular proliferation. Vascular endothelial growth factor (VEGF), the main mediator of angiogenesis, and platelet-derived growth factor receptor-β (PDGFR-β), receptor for the potent mitogen PDGF, are two indicators of the angiogenic potential of human gliomas. We studied a series of 57 surgical biopsies of astrocytic neoplasms by immunohistochemistry to elucidate the relationship between tumor proliferation, quantified as Ki67-LI, and the expression of these two proteins.
Ki67-LI increases throughout histological malignancy, although staining in endothelial cells has rarely been recorded. Elevated amounts of VEGF-positive tumor cells (VEGF-LI) were found in anaplastic astrocytomas and glioblastomas, mainly around areas of necrosis, cysts, or edema. Endothelium of blood vessels was consistently stained. PDGFR-β positivity was found in glomeruloid formations and in tumor cells, excluding pilocytic astrocytomas. Multinucleated giant cells and perivascular tumor cells were positive in glioblastomas. In addition, peritumoral microglia-like cells were also stained in some cases. Statistical correlation was only found between PDGFR-β and Ki67 LIs. In conclusion, VEGF as permeability factor is involved in the development of secondary neoplastic changes, whereas PDGFR-β is directly correlated to proliferation indexes. Strong expression of VEGF and PDGFR-β found in endothelium and tumor cells would seem to support a combined role in tumoral neoangiogenesis
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Berkman R. A., Merrill M. J., Reinhold W. C., Monacci W. T., Saxena A., Craig C. W., et al. (1993) Expression of the vascular permeability factor/vascular endothelial growth factor gene in central nervous system neoplasms. J. Clin. Invest. 91, 153–159.
Brock T. A., Dvorak H. F., and Senger D. R. (1991) Tumour-secreted vascular permeability factor increases cytosolic Ca2+ and von Willebrand factor release in human endothelial cells. Am. J. Pathol. 138, 213–221.
Conolly D. T., Heuvelman D. M., Nelson R., Olander J. V., Eppley B. L., Delfino J. J., et al. (1989) Tumour vascular permeability factor stimulates endothelial cell growth and angiogenesis. J. Clin. Invest. 84, 1470–1478.
Dvorak H. F., Brown L. F., Detmar M., and Dvorak A. M. (1995) Vascular permeability factor/vascular endothelial growth factor, microvascular permeability and angiogenesis. Am. J. Pathol. 46, 1029–1039.
Ferrara N. and Henzel W. J. (1989) Pituitary follicular cells secrete a novel heparin-binding growth factor specific for vascular endothelial cells. Biochem. Biophys. Res. Commun. 161, 851–859.
Folkman J. (1995) Angiogenesis in cancer, vascular, rheumathoid and other disease. Nature Med. 1, 27–31.
Gerdes J., Lemke H., Baisch H., Wacker H. H., Schwab U., and Stein H. (1984) Cell cycle analysis of a cell proliferation-associated human nuclear antigen defined by the monoclonal antibody Ki-67. J. Immunol. 33, 1710–1715.
Gerdes J., Schlueter C., and Duchrow M. (1991) Immunobiochemical and molecular biologic characterization of the cell proliferation-associated nuclear antigen that is defined by monoclonal antibody Ki-67. Am. J. Pathol. 138, 867–873.
Hanks S. K., Quinn A. M., and Hunter T. (1988) The protein kinase family: conserved features and deduced phylogeny of the catalytic domains. Science 241, 42–52.
Hatva E., Kaipainen A., Mentula P., Jääskeläinen J., Paetau A., Haltia M., and Alitalo K. (1995) Expression of endothelial cell-specific receptor tyrosine kinases and growth factors in human brain tumors. Am. J. Pathol. 146, 368–378.
Hermansson M., Nister M., Betsholz C., Heldin C. H., Westermark B., and Funa K. (1988) 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 5, 7748–7752.
Inaba T., Shimano H., Gotoda T., Harada K., Shimada M., Ohsuga J., et al. (1993) Expression of platelet-derived growth factor beta receptor on human monocyte-derived macrophagues and effects of platelet-derived growth factor BB dimer on cellular function. J. Biol. Chem. 268, 24,353–24,360.
Key G., Petersen J. I., Becker M. H., Duchrow M., Schluter C., Askaa J., et al. (1993) New antiserum against Ki67 antigen suitable for double immunostaining of paraffin wax sections. J. Clin. Pathol. 46, 1080–1084.
Kleihues P., Burger P. C., and Scheithauer B. W. (1993) The new WHO classification of brain tumours. Brain Pathol. 3, 255–268.
Lafuente J. V., Adán B., Alkiza K., Rossi M., and Cruz-Sánchez F. F. (1995) Vascular proliferation and related changes in the vessel wall of brain tumors. J. Neuropathol. Exp. Neurol. 54(S), S80.
Nakamura T., Takeshita I., Inamura T., Tashima T., and Fukui M. (1993) Expression of the B-chain of platelet-derived growth factor and proliferative activity of human brain tumors. Neurol. Med. Chir. Tokyo 33, 205–211.
Pepper M. S., Ferrara N., Orci L., and Montesano R. (1991) Vascular endothelial growth factor (VEGF) induces plasminogen activators and plasminogen activator inhibitor-1 in microvascular endothelial cells. Biochem. Biophys. Res. Comm. 181, 902–906.
Plate K. H., Breier G., Farrell C. L., and Risau W. (1992) Platelet-derived growth factor receptor-b is induced during tumor development and upregulated during tumor progression in endothelial cells in human gliomas. Lab. Invest. 67, 529–534.
Plate K. H., Breier G., Weich H. A., and Risau W. (1992) Vascular endothelial growth factor is a potential tumor angiogenesis factor in human gliomas in vivo. Nature 359, 845–848.
Plate K. H., Breier G., Weich H. A., Mennel H. D., and Risau W. (1994) VEGF and glioma angiogenesis: coordinate induction of VEGF receptors, distribution of VEGF protein and possible in vivo regulatory mecahisms. Int. J. Cancer 59, 520–529.
Russell D. C. and Rubinstein L. J. (1989). Pathology of Tumors of the Nervous System, 5th ed. Edward Arnold, London.
Schweiki D., Itin A., Soffer D., and Keshet E. (1992) Vascular endothelial growth factor induced by hypoxia may mediate hypoxia-initiated angiogenesis. Nature 359, 843–845.
Strugar J. G., Criscuolo G. R., Rothbart D., and Harrington W. N. (1995) Vascular endothelial growth/permeability factor expression in human glioma specimens: correlation with vasogenic brain edema and tumor-associated cysts. J. Neurosurg. 83, 682–689.
Tischer E., Mitchell R., Hartman T., Silva M., Gospodarowicz D., Fiddes J. C., et al. (1991) The human gene for vascular endothelial growth factor. J. Biol. Chem. 266, 11,947–11,954.
Tsai J. C., Goldman C. K., and Gillespie G. Y. (1995) Vascular endothelial growth factor in glioma cell lines: induced secretion by EGF, PDGF-BB and bFGF. J. Neurosurg. 82, 864–873.
Unemori E. N., Ferrara N., Bauer E. A., and Amento E. P. (1992) Vascular endothelial growth factor induces interstitial collagenase expression in human endothelial cells. J. Cell. Physiol. 153, 557–562.
Verheijen R., Kuipers H. J. H., and Schlingemann R. O. (1989) Ki-67 detects a nuclear matrix-associated proliferation-related antigen. J. Cell. Sci. 92, 123–130.
Weindel K., Moringlane J. R., Marme D., and Weich H. A. (1994) Detection and quantification of vascular endothelial growth factor/vascular permeability factor in brain tumor tissue and cyst fluid: the key to angiogenesis? Neurosurgery 35, 439–449.
Weller M., Heimann K., and Wiedemann P. (1990) The pathogenesis of vitreoretinal proliferation and traction: a working hypothesis. Med. Hypotheses 31, 157–159.
Wesseling P., Schlingemann R. O., Rietveld F. J. R., Link M., Burger P. C., and Ruiter D. J. (1995) 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.
Zülch K. J. (1979) Histological typing of tumours of the central nervous system, in International Histological Classification of Tumors, vol. 21. World Health Organization, Geneva.
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Lafuente, J.V., Adán, B., Alkiza, K. et al. Expression of vascular endothelial growth factor (VEGF) and platelet-derived growth factor receptor-β (PDGFR-β) in human gliomas. J Mol Neurosci 13, 177–185 (1999). https://doi.org/10.1385/JMN:13:1-2:177
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DOI: https://doi.org/10.1385/JMN:13:1-2:177