Abstract
A total of 14 surgical specimens, including 7 glioblastomas, 3 anaplastic astrocytomas, 2 brains adjacent to glioblastoma and 2 grossly normal brains, were investigated immunohistochemically for the expression of antithrombin III (AT-III), heparan sulfate proteoglycan (HSPG) and thrombomodulin (TM) in the endothelium of microvessels. The immunoreaction to AT-III was of moderate intensity in grossly normal brains, brains adjacent to glioblastoma, and anaplastic astrocytomas, but was only weak in glioblastomas, especially in the capillaries. The immunoreaction to HSPG was constantly intense in the microvessels in all the specimens. Although the immunoreaction to TM was negative or only faint in the microvessels in grossly normal brains, it was moderately to strongly intense in anaplastic astrocytomas and brains adjacent to glioblastoma. The intensity of immunoreaction to TM was variable, from faint to strong in the capillaries, and moderate to strong in larger microvessels in glioblastomas. The present study suggested that the alterations in the expression of those antithrombotic molecules could explain, at least in part, the tendencies for intratumoral hemorrhage as well as intravascular thrombosis in the different areas of malignant gliomas.
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Colman RW, Marder VJ, Salzman EW, Hirsh J (1987) Overview of hemostasis. In: Colman RW, Hirsh J, Marder VJ, Salzman EW (eds) Hemostasis and thrombosis: basic principles and clinical practice, 2nd edn. J. B. Lippincott, Philadelphia, pp 3–17
de Agostini AI, Watkins SC, Slayter HS, Youssoufian H, Rosenberg RD (1990) Localization of anticoagulantly active heparan sulfate proteoglycans in vascular endothelium: antithrombin binding on cultured endothelial cells and perfused rat aorta. J Cell Biol 111: 1293–1304
Deschepper CF, Bigornia V, Berens ME, Lapointe MC (1991) Production of thrombin and antithrombin III by brain and astroglial cell cultures. Mol Brain Res 11: 355–358
Engel U (1992) Zur Morphologie von Hämostasestörungen in gliösen Hirntumoren. Acta Histochem 42: 201–210
Esmon CT (1987) The regulation of natural anticoagulant pathways. Science 235: 1348–1352
Esmon NL (1989) Thrombomodulin. In: Coller BS (ed) Progress in hemostasis and thrombosis. W. B. Saunders, Philadelphia, pp 29–55
Gallagher JT (1989) The extended family of proteoglycans: social residents of the pericellular zone. Curr Opin Cell Biol 1: 1201–1218
Giddings JC (1988) Molecular genetics and immunoanalysis in blood coagulation. Ellis Horwood, Chichester, pp 143–157
Hassel JR, Kimura JH, Hascal VC (1986) Proteoglycan core protein families. Annu Rev Biochem 55: 539–567
Hook M, Kjellen L, Johannson S, Robinson J (1984) Cell surface glycosaminoglycans. Annu Rev Biochem 53: 847–869
Ishii H, Salem HH, Bell CE, Laposata EA, Majerus PW (1986) Thrombomodulin, an endothelial anticoagulant protein, is absent from the human brain. Blood 67: 362–365
Ishii H, Nakano M, Tsubouchi J, Ishikawa T, Uchiyama H, Hiraishi S, Tahara C, Miyajima Y, Kazama M (1990) Establishment enzyme immunoassay of human thrombomodulin in plasma and urine using monoclonal antibodies. Thromb Haemostat 63: 157–162
Jaffe EA (1991) Endothelial cell structure and function. In: Hoffman R, Benz EJ, Shattil SJ, Furie B, Cohen HJ (eds) Hematology: basic principles and practice. Churchill Livingstone, New York, pp 1198–1213
Kondziolka D, Bernstein M, Resch L, Tator CH, Fleming JFR, Vanderlinden RG, Schutz H (1987) Significance of hemorrhage into brain tumors: clinicopathological study. J. Neurosurg 67: 852–857
Lee AKY, Chan V, Chan TK (1979) The identification and localization of antithrombin III in human tissues. Thromb Res 14: 209–217
Lindblom A, Bengtsson G Olivecrona, Fransson LA (1991) Domain structure of endothelial heparan sulphate. Biochem J 279: 821–829
Liwnicz BH, Wu SZ, Tew JM Jr (1987) The relationship between the capillary structure and hemorrhage in gliomas. J. Neurosurg. 66: 536–541
Marcum JA, Reilly CF, Rosenberg RD (1986) The role of specific forms of heparan sulfate in regulating blood vessel wall function. In: Coller BS (ed) Progress in hemostasis and thrombosis. Grune & Stratton, Orlando, pp 185–215
Maruyama I, Bell CE, Majerus PW (1985) Thrombomodulin is found on endothelium of arteries, veins, capillaries and lymphatics, and on synytiotrophoblast of human placenta. J Cell Biol 101: 363–371
Shimada K, Kobayashi M, Kimura S, Nishinaga M, Takruchi K, Ozawa T (1991) Anticoagulant heparin-like glycosaminoglycans on endothelial cell surface. Jpn Circ J 55: 1016–1021
Steck PA, Moser RP, Bruner JM, Liang L, Freidman AN, Hwang TL, Young WKA (1989) Altered expression and distribution of heparan sulfate proteoglycans in human gliomas. Cancer Res 49: 2096–2103
Wong VLY, Hofman FM, Ishii H, Fisher M (1991) Regional distribution of thrombomodulin in human brain. Brain Res 556: 1–5
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Supported in part by the Grant-in-Aid for Cancer Research (4-23) from the Japanese Ministry of Health and Welfare
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Isaka, T., Yoshimine, T., Maruno, M. et al. Altered expression of antithrombotic molecules in human glioma vessels. Acta Neuropathol 87, 81–85 (1994). https://doi.org/10.1007/BF00386257
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DOI: https://doi.org/10.1007/BF00386257