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Glomeruloid blood vessels in ethylnitrosourea-induced rat gliomas

Histological and immunohistochemical studies

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Summary

Glomeruloid blood vessels (GBVs), a characteristic histological feature of most human malignant gliomas, were recognized with high incidence in autochthonous rat gliomas induced by transplacental administration of ethylnitrosourea. To evaluate some of the biological properties of these GBVs, we carried out a study using histological methods and immunohistochemical staining for glial fibrillary acidic protein, factor VIII-related antigen (VIII Ag) and bromodeoxyuridine (BrdUrd). Of 22 animals with large, massively growing gliomas in the CNS, GBVs including conglomerate aggregations of small blood vessels with endothelial hyperplasia and strong VIII Ag expression were observed in 13 large gliomas histologically consisting of primitive neuroepithelial neoplasms (PNN; so called ependymoma) and mixed-type gliomas in combination with astrocytoma and PNN or anaplastic astrocytoma. The anaplastic gliomas in our series were devoid of GBVs. These findings indicate that GBV formation takes place in a histological variety of experimental gliomas. Furthermore, the GBVs were frequently associated with the vasculo-mesenchymal stroma in the parent gliomas, suggesting an intimate relationship with the morphogenesis of GBVs. In addition, it was shown that the GBVs had a higher BrdUrd-labelling index than that of other blood vessels in gliomas and also that of neoplastic cells in most parent gliomas, except for anaplastic gliomas. Based on these results, the possible mechanism of GBV morphogenesis is discussed with regard to the roles of macromolecules in the induction and regulation of GBVs.

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References

  1. Abrahamson DR (1986) Recent studies on the structure and pathology of basement membranes. J Pathol 149:257–278

    Google Scholar 

  2. Buck CA, Horwitz AF (1987) Cell surface receptors for extracellular matrix molecules. Annu Rev Cell Biol 3:179–205

    Google Scholar 

  3. Calvo W (1971) Growth patterns of intracranial neoplasms. In: Minckler J (ed) Pathology of the nervous system, vol 2. McGraw-Hill, New York, pp 1960–1976

    Google Scholar 

  4. Copeland DD, Vogel FS, Bigner DD (1975) The induction of intracranial neoplasms by the inoculation of avian sarcoma virus in perinatal and adult rats. J Neuropathol Exp Neurol 34:340–358

    Google Scholar 

  5. Deane BR, Papp MI, Lantos PL (1984) The vasculature of experimental brain tumors. Part 3. Permeability studies. J Neurol Sci 65:47–58

    Google Scholar 

  6. Esch F, Baird A, Ling N, Ueno N, Hill F, Denoroy L, Klepper R, Gospodarowicz D, Böhlen P, Guillemin R (1986) Primary structure of bovine pituitary basic fibroblast growth factor (FGF) and comparison with the amino-terminal sequence of bovine brain acidic FGF. Proc Natl Acad Sci USA 82:6507–6511

    Google Scholar 

  7. Fett JW, Strydom DJ, Lobb RR, Alderman EM, Bethune JL, Riordan JF, Vallee BL (1985) Isolation and characterization of angiogenin, and angiogenic protein from human carcinoma cells. Biochemistry 24:5480–5486

    Google Scholar 

  8. Folkman J, Ingber DE (1987) Inhibitors of angiogenesis: angiostatic steroids. In: Rifkin DB, Klagsbrun M (eds) Angiogenesis, mechanisms and pathobiology. Cold Spring Harbor Laboratory, Cold Spring Harbor, pp 95–100

    Google Scholar 

  9. Fujita T (1984) Vascularization in infantile brain tumors induced by human adenovirus type 12 in rats. Acta Pathol Jpn 34:1343–1354

    Google Scholar 

  10. Greene HSN, Harvey EK (1968) The development of sarcomas from transplants of the hyperplastic stromal endothelium of glioblastoma multiforme. Am J Pathol 53:483–499

    Google Scholar 

  11. Groothuis DR, Fischer JM, Vick NA, Bigner DD (1980) Experimental gliomas: an autoradiographic study of the endothelial component. Neurology 30:297–301

    Google Scholar 

  12. Hsu SM, Raine L, Fanger H (1981) Use of avidin-biotinperoxidase complex (ABC) in immunoperoxidase technique: a comparison between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem 29:577–580

    Google Scholar 

  13. Jänisch W, Rath FW (1979) Early stages of brain tumor development in experimental chemical carcinogenesis. Prog Neuropathol 4:215–233

    Google Scholar 

  14. Koestner A, Swenberg JA, Wechsler W (1971) Transplacental production with ethylnitrosourea of neoplasms of the nervous system in Sprague-Dawley rats. Am J Pathol 63:37–58

    Google Scholar 

  15. Kumanishi T, Ikuta F, Yamamoto T (1973) Brain tumors induced by Rous sarcoma virus, Schmidt-Ruppin strain. III. Morphology of brain tumors induced in adult mice. J Natl Cancer Inst 50:95–109

    Google Scholar 

  16. Lantos PL (1980) Chemical induction of tumours in the nervous system. In: Thomas DGT, Graham DI (eds) Brain tumors. Scientific basis, clinical investigation and current therapy. Butterworths, London, pp 85–108

    Google Scholar 

  17. Luthert PJ, Lantos PL (1985) A morphometric study of the microvasculature of a rat glioma. Neuropathol Appl Neurobiol 11:461–473

    Google Scholar 

  18. Mandybur TI, Alvira MM (1982) Ultrastructural findings in so-called ependymal rat tumors induced by transplacental administration of ethylnitrosourea (ENU). Acta Neuropathol (Berl) 57:51–58

    Google Scholar 

  19. Manuelidis EE (1966) The fate of serial heterologously transplanted glioblastoma multiforme in the eye of the guinea pig. Am J Pathol 48:65–89

    Google Scholar 

  20. McComb RD, Moul JM, Bigner DD (1987) Distribution of type VI collagen in human glioma. Comparison with fibronecting and glioma-mesenchymal matrix glycoprotein. J Neuropathol Exp Neurol 46:623–633

    Google Scholar 

  21. Nyström S (1960) Pathological changes in blood vessels of human glioblastoma multiforme. Comparative studies using plastic casting, angiography, light microscopy and electron microscopy, and with reference to some other brain tumors. Acta Pathol Microbiol Scand [Suppl 137] 49:9–83

    Google Scholar 

  22. Onda K, Tanaka R, Washiyama K, Takeda N, Kumanishi T (1988) Correlation of DNA ploidy and morphological features of human glioma cell cultures with the establishment of cell lines. Acta Neuropathol 76:433–440

    Google Scholar 

  23. Pakula H, Mennet HD, Zülch KJ (1978) Gross vascularization of experimentally induced transplanted tumors of the central and peripheral nervous system. Acta Neuropathol (Berl) 43:185–190

    Google Scholar 

  24. Russel DS, Rubinstein LJ (1989) Pathology of tumours of the nervous system, 4th edn. Edward Arnold, London, pp 219–247

    Google Scholar 

  25. Schreiber AB, Winkler ME, Derynck R (1986) Transforming growth factor-α: a more potent angiogenic mediator than epidermal growth factor. Science 232:1250–1253

    Google Scholar 

  26. Shing V, Folkman J, Sullivan R, Butterfield C, Murray J, Klagsbrun M (1984) Heparin affinity: purification of a tumor-derived capillary endothelial growth factor. Science 223:1296–1299

    Google Scholar 

  27. Sholley MM, Cavallo T, Cortran RS (1977) Endothelial proliferation in inflammation. I. Autoradiographic studies following thermal injury to the skin of normal rats. Am J Pathol 89:277–296

    Google Scholar 

  28. Sorszegi P, Molnár L, Modis K (1976) Morphologic differences between tumorous and normal brain vessels. In: Cervós-Navarro J, Betz E, Matakas F, Wüllenweber R (eds) The cerebral vessel wall. Raven Press, New York, pp 75–81

    Google Scholar 

  29. Swenberg JA, Koestner A, Wechsler W (1972) The induction of tumors of the nervous system with intravenous methylnitrosourea. Lab Invest 26:74–85

    Google Scholar 

  30. Tannock IF, Hayashi S (1972) The proliferation of capillary endothelial cells. Cancer Res 32:77–82

    Google Scholar 

  31. Thomas KA, Rios-Candelore M, Gimenez-Gallego G, DiSalvo J, Bennett C, Rodkey J, Fitxpatrick S (1985) Pure brain-derived acidic fibroblast growth factor is a potent angiogenic vascular endothelial cell mitogen with sequence homology to interleukin 1. Proc Natl Acad Sci USA 82:6409–6413

    Google Scholar 

  32. Towbin H, Staehelin T, Gordon J (1979) Electrophoretic transfer of protein from polyacrylamide gels to nitrocellulose sheets. Procedure and some application. Proc Natl Acad Sci USA 76:4350–4354

    Google Scholar 

  33. Vick NA (1980) Brain tumor microvasculature. In: Weiss L, Gilbert HA, Posner JB (eds) Brain metastasis, vol II, M Nijhoff, Boston, pp 115–133

    Google Scholar 

  34. Weller RO, Foy M, Cox S (1977) The development and ultrastructure of the microvasculature in malignant gliomas. Neuropathol Appl Neurobiol 3:307–322

    Google Scholar 

  35. Wright RL (1963) Neovascularization in experimental gliomas. J Neuropathol Exp Neurol 22:435–445

    Google Scholar 

  36. Yoshida Y, Ikuta F (1988) Microvasculature in experimental glioma and developing brain, rat. In: Jones TC, Mohr U, Hunt RD (eds) Nervous system. Springer, Heidelberg, pp 1–6

    Google Scholar 

  37. Yoshida Y, Yamada M, Wakabayashi K, Ikuta F (1987) Immunohistochemical detection of DNA replicating cells in the developing nervous system: use of bromodeoxyuridine and its monoclonal antibody to rat fetuses. Biomed Res 8:431–444

    Google Scholar 

  38. Zülch KJ (1965) Brain tumors. Their biology and pathology. Springer, New York, pp 147–177

    Google Scholar 

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Supported in part by grants nos. 63570675 and 01480350 from the Ministry of Education, Science and Culture, Japan, and by a grant from the Ministry of Health and Welfare, Japan

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Yoshida, Y., Kumanishi, T., Abe, S. et al. Glomeruloid blood vessels in ethylnitrosourea-induced rat gliomas. Acta Neuropathol 79, 240–247 (1989). https://doi.org/10.1007/BF00294657

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