Summary
Two thorium dioxide-induced murine hemangioendotheliomas, 42021 TCT and 44347 TST, were grown subcutaneously (for up to 22 and 15 passages respectively) or intracranially (single passage) and were adapted to culture as a monolayer and, in a limited fashion, in an organ culture system or in rotary suspension. They remained viable and malignant following 20–21 years of storage in liquid nitrogen, and had ultrastructural similarities to human hemangioblastomas. The murine tumors were positive for Griffonia (Bandeiraea) simplicofolia isolectin B4 binding, establishing their endothelial nature; however, unlike human hemangioblastic tumors, they did not cross-react with antisera to human factor VIII or fibronectin and they did not demonstrate Ulex europaeus type I lectin (UEA I) binding (as is also the case for non-neoplastic murine vascular endothelial cells). A variety of morphological cell types in cultures derived from the tumors were also positive for Griffonia (Bandeiraea) simplicifolia isolectin B4 binding. Both murine hemangioendotheliomas, when implanted in the cerebrum, were potent inducers of reactive gliosis, but there was no evidence of uptake of glial fibrillary acidic protein. Unlike the human cerebellar hemangioblastomas, murine tumors were malignant and invasive and did not contain stromal cells, nor did they demonstrate Weibel-Palade bodies or extensive pinocytotic activity. Thus, the murine tumors appear to more closely resemble angiosarcomas or epitheloid hemangioblastomas than the cerebellar hemangioblastomas.
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Angervall L, Karlsson K, Kindblom L-G, Stener B (1985) Atypical hemangiendothelioma of venous origin. Am J Surg Pathol 9:504–516
Auerbach R, Alby L, Grieves J, Joseph J, Lindgren C, Morrissey LW, Sidky YA, Tu M, Watt SL (1982) Monoclonal antibody against angiotensin-converting enzyme: its use as a marker for murine, bovine, and human endothelial cells. Proc Natl Acad Sci USA 79:7891–7895
Ault KA, Springer TA (1981) Cross-reaction of a rat antimouse phagocyte-specific monoclonal antibody (anti-Mac-1) with human monocytes and natural killer cells. J Immunol 126:359–364
Böhling T, Paetau A, Ekblom P, Haltia M (1983) Distribution of endothelial and basement membrane markers in angiogenic tumors of the nervous system. Acta Neuropathol (Berl) 62:67–72
Burgdorf WHC, Mukai K, Rosai J (1981) Immunobistochemical identification of factor VIII-related antigen in endothelial cells of cutaneous lesions of alleged vascular nature. Am J Clin Pathol 75:167–171
Charman HP, Lowenstein DH, Cho KG, DeArmond SJ, Wilson CB (1988) Primary cerebral angiosarcoma: Case report. J Neurosurg 68:806–810
Crouch E, Balian G, Holbrook K, Duksin D, Bornstein P (1978) Amniotic fluid fibronectin. Characterization and synthesis by cells in culture. J Cell Biol 78:701–715
Cruz-Sánchez FF, Rossi ML, Rodriguez S, Nakamura N, Hughes JT, Coakham HB (1990) Haemangioblastoma: histological and immunohistological study of an enigmatic cerebellar tumour. Histol Histopathol 5:407–413
Deck JHN, Rubinstein LJ (1981) Glial fibrillary acidic protein in stromal cells of some capillary hemangioblastomas: significance and possible implications of an immunoperoxidase study. Acta Neuropathol (Berl) 54:173–181
Dropulié B, Masters CL (1987) Culture of mouse brain capillary endothelial cell lines that express factor VIII, γ-glutamyl transpeptidase, and form junctional complexes in vitro. In Vitro Cell Dev Biol 23:775–781
Epstein JI, White CL III, Mendelsohn G (1984) Factor VIII-related antigen and glial fibrillary acidic protein immunoreactivity in the differential diagnosis of central nervous system hemangioblastomas. Am J Clin Pathol 81:285–292
Fisher ER, Kaufman N, Mason EJ (1952) Hemangiopericytoma: histologic and tissue culture studies. Am J Pathol 28:653–661
Gimbrone MA Jr, Fareed GC (1976) Transformation of cultured human vascular endothelium by SV40 DNA. Cell 9:685–693
Grinspan JB, Mueller SN, Levine EM (1983) Bovine endothelial cells transformed in vitro by benzo(a)pyrenc. J Cell Physiol 114:328–338
Ho K-L (1984) Ultrastructure of cerebellar capillary hemangioblastoma. I. Weibel-Palade bodies and stromal cell histogenesis. J Neuropathol Exp Neurol 43:592–608
Ho K-L (1984) Ultrastructure of cerebellar capillary hemangioblastoma. II. Mast cells and angiogenesis. Acta Neuropathol (Berl) 64:308–318
Ho K-L (1987) Ultrastructure of cerebellar capillary hemangioblastoma. VI. Concentric lamellar bodies of endoplasmic reticulum in stromal cells. Acta Neuropathol (Berl) 74:345–353
Ho M-K, Springer TA (1982) Mac-1 antigen: quantitative expressions in macrophage populations and tissues, and immunofluorescent localization in spleen. J Immunol 128:2281–2286
Holt SC, Brumer JM, Ordóñez NG (1986) Capillary hemangioblastomas. An immunohistochemical study. Am J Clin Pathol 86:423–429
Holthöfer H (1983) Lectin binding sites in kidney: a comparative study of 14 animal species. J Histochem Cytochem 31:531–537
Holthöfer H, Virtanen I, Kariniemi A-L, Hormia M, Linder E, Miettinen A (1982) Ulex europaeus I lectin as a marker for vascular endothelium in human tissues. Lab Invest 47:60–66
Hosaka M, Murase N, Orito T, Mori M (1985) Immunohistochemical evaluation of factor VIII-related antigen, filament proteins and lectin binding in haemangiomas. Virchows arch [a] 407:237–247
Kepes JJ, Rengachary SS, Lee SH (1979) Astrocytes in hemangioblastomas of the central nervous system and their relationship to stromal cells. Acta Neuropathol (Berl) 47:99–104
Kepes JJ, Rubinstein LJ, Maw G, Burdick B (1986) Epithelioid hemangiomas (hemangioendotheliomas) of the central nervous system and its coverings, a report of three cases. J Neuropathol Exp Neurol 45:319
Kindblom LG (1982) Factor VIII-related antigen and mast cells. Acta Pathol Microbiol Immunol Scand [A] 90:437–439
Kochi N, Tani E, Kaba K, Natsume S (1984) Immunohistochemical study of fibronectin in hemangioblastomas and hemangiopericytomas. Acta Neuropathol (Berl) 64:229–233
Little D, Said JW, Siegel RJ, Fealy M, Fishbein MC (1986) Endothelial cell markers in vascular neoplasms: an immunohistochemical study comparing factor VIII-related antigen, blood group specific antigens, 6-keto-PGF1 alpha, and Ulex europaeus I lectin. J Pathol 149:89–95
Maddox DE, Shibata S, Goldstein IJ (1982) Stimulated macrophages express a new glycoprotein receptor reactive with Griffonia simplicifolia I-B4 isolectin. Proc Natl Acad Sci USA 79:166–170
Mena H, Ribas JL, Enzinger FM, Parisi JE (1991) Primary angiosarcoma of the central nervous system: study of eight cases and review of the literature. J Neurosurg 75:73–76
Mukai K, Rosai J, Burgdorf WHC (1980) Localization of factor VIII-related antigen in vascular endothelial cells using an immunoperoxidase method. Am J Surg Pathol 4:273–276
Murray AB (1987) Weibel-Palade bodies are not reliable ultrastructural markers for mouse endothelial cells. Lab Animal Sci 37:483–485
Obeso J, Weber J, Auerbach R (1990) A hemangioendothelioma — derved cell line: its use as a model for the study of endothelial cell biology. Lab Invest 63:259–269
Ordóñez NG, Batsakis JG (1984) Comparison of Ulex europaeus I lectin and factor VIII-related antigen in vascular lesions., Arch Pathol Lab Med 108:129–132
Piovella F, Nall G, Malamani GS, Majolino I, Frassoni F, Sitar GM, Ruggeri A, Dell'Orbo C, Ascari E (1978) The ultrastructural localization of factor VIII-antigen in human platelets, megakaryocytes and endothelial cells utilizing a ferritinlabelled antibody. Br J Haematol 39:209–213
Robinson RA, TenEyck CJ, Hart MN (1986) Methods in laboratory investigation. Establishment and preliminary growth characteristics of a transformed mouse cerebral microvessel endothelial cell line. Lab Invest 54:579–588
Rubinstein LJ, Herman MM, Foley VL (1973) In vitro characteristics of human glioblastomas maintained in organ culture systems. Light microscopy observations. Am J Pathol 71:61–80
Sahagun G, Moore SA, Fabry Z, Shelper RL, Hart MN (1989) Purification of murine endothelial cell cultures by flow cytometry using fluorescein-labeled Griffonia simplicifolia agglutinin. Am J Pathol 134:1227–1232
Schelper RL, Olson SP, Carroll TJ, Hart MN, Witters E (1986) Studies of the endothelial origin of cells in systemic angioendotheliomatosis and other vascular lesions of the brain and meninges using Ulex europaeus lectin stain. Clin Neuropathol 5:231–237
Schulte BA, Spicer SS (1983) Histochemical evaluation of mouse and rat kidneys with lectin-horseradish peroxidase conjugates. Am J Anat 168:345–362
Sehested M, Hou-Jenson K (1981) Factor VIII-related antigen as an endothelial cell marker in benign and malignant diseases. Virchows Arch [A] 391:217–225
Spence AM, Rubinstein LJ (1975) Cerebellar capillary hemangioblastoma: its histogenesis studied by organ culture and electron microscopy. Cancer 35:326–341
Springer T, Galfré G, Secher DS, Millstein C (1979) Mac-1: a macrophage differentiation antigen identified by monoclonal antibody. Eur J Immunol 9:301–306
Swarm RL, Miller E, Michelitch HJ (1962) Malignant vascular tumors in rabbits injected intravenously with colloidal thorium dioxide. Pathol Microbiol 25:27–44
Tanimura A, Nakamura Y, Hachisuka H, Tanimura Y, Fukumura A (1984) Hemangioblastoma of the central nervous system: nature of the stromal cells as studied by the immunoperoxidase technique. Hum Pathol 15:866–869
Taratuto AL, Zurbriggen G, Sevlever G, Saccoliti M (1988) Epithelioid hemangioendothelioma of the central nervous system. Pediatr Neurosci 14:11–14
Toda K-I, Tsujioka K, Maruguchi Y, Ishii K, Miyachi Y, Kuribayashi K, Imamura S (1990) Establishment and characterization of tumorigenic murine vascular endothelial cell line (F-2). Cancer Res 50:5526–5530
VandenBerg SR, Ludwin SK, Herman MM (1976) In vitro astrocytic differentiation from embryoid bodies of an experimental mouse testicular teratoma. Am J Pathol 83:197–212
Vinores SA, Herman MM, Rubinstein LJ, Marangos PJ (1984) Electron microscopic localization of neuron-specific enolase in rat and mouse brain. J Histochem Cytochem 32:1295–1302
Weber T, Seitz RJ, Liebert UG, Gallasch E, Wechsler W (1985) Affinity cytochemistry of vascular endothelia in brain tumors by biotinylated Ulex europaeus type I lectin (UEA I). Acta Neuropathol (Berl) 67:128–135
Weiss SW, Enzinger FM (1982) Epithelioid hemangioendothelioma: a vascular tumor often mistaken for a carcinoma. Cancer 50:970–981
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Supported by National Cancer Institute Research Grant CA 31271 and Graduate Neuropathology Training Grant T32 NS 7236 from the National Institute of Neurological and Communicative Diseases and Stroke, U.S. Department of Health and Human Services. E.P. was supported by a grant from the Foundation Suisse de Bourses de Médecine et Biologie and C.T. was partly supported by an American Cancer Society Fellowship (85-43)
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Vinores, S.A., Herman, M.M., Perentes, E. et al. The growth of two murine hemangioendotheliomas intracranially, subcutaneously, and in culture, and their comparison with human cerebellar hemangioblastomas: morphological and immunohistochemical studies. Acta Neuropathol 84, 67–77 (1992). https://doi.org/10.1007/BF00427217
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DOI: https://doi.org/10.1007/BF00427217