Abstract
Vascular endothelial growth factor (VEGF) is a potent angiogenic factor in human gliomas. VEGF-induced proteins in endothelial cells, tissue factor (TF), osteopontin (OPN) and αvβ3 integrin have been implicated as important molecules by which VEGF promotes angiogenesis in vivo. Sixty-eight gliomas were immunohistochemically stained with TF, VEGF, OPN and αvβ3 integrin antibody. Twenty-three tumours, six normal brains and nine glioma cell lines were evaluated for their mRNA expression of VEGF and TF by reverse transcription polymerase chain reaction analysis. The data indicated that TF as well as VEGF was a strong regulator of human glioma angiogenesis. First, TF expression in endothelial cells which was observed in 74% of glioblastomas, 54% of anaplastic astrocytomas and none of low-grade astrocytomas, correlated with the microvascular density of the tumours. Double staining for VEGF and TF demonstrated co-localization of these two proteins in the glioblastoma tissues. Second, there was a correlation between TF and VEGF mRNA expression in the glioma tissues. Third, glioma cell conditioned medium containing a large amount of VEGF up-regulated the TF mRNA expression in human umbilical vein endothelial cells. OPN and αvβ3 integrin, were also predominantly observed in the microvasculature of glioblastomas associated with VEGF expression. Microvascular expression of these molecules could be an effective antiangiogenesis target for human gliomas. © 2000 Cancer Research Campaign
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References
Brem S, Cotran SS and Folkman J (1972) Tumor angiogenesis: a quantitative method for histological grading. J Natl Cancer Inst 48: 347–356
Brooks PC, Clark RAF and Cheresh DA (1994a) Requirement of vascular integrin αvβ3 for angiogenesis. Science 264: 569–571
Brooks PC, Montgomery AMP, Rosenfeld M, Reisfeld RA, Hu T, Klier G and Cheresh DA (1994b) Integrin αvβ3 antagonists promote tumor regression by inducing apoptosis of angiogenic vessels. Cell 79: 1157–1164
Brown LF, Papadopoulos-Sergiou A, Berse B, Manseau EJ, Tognazzi K, Perruzzi CA, Dvorak HF and Senger DR (1994) Osteopontin expression and distribution in human carcinomas. Am J Pathol 145: 610–623
Carmeliet P, Macknan N, Mooms L, Luther T, Gressens P, Van Vlaenderen I, Demunck H, Kasper M, Breier G, Evrard P, Muller M, Risau W, Edginton T and Collen D (1996) Role of tissue factor in embryonic blood vessel development. Nature 383: 73–75
Contrino J, Hair G, Kreutzer DL and Ricklcs FR (1996) In situ detection of tissue factor in vascular endothelial cells: correlation with the malignant phenotype of human breast disease. Nat Med 2: 209–215
Dvorak HF, Brown LF, Detmar M and Dvorak AM (1995) Vascular permeability factor/vascular endothelial growth factor, microvascular hyperpermeability, and angiogenesis. Am J Pathol 146: 1029–1039
Folkman J and Shing Y (1992) Mini-review: angiogenesis. J Biol Chem 267: 10931–10934
Gladson CL (1996) Expression of integrin αvβ3 in small blood vessels of glioblastoma tumors. J Neuropathol Exp Neurol 55: 1143–1149
Hamada K, Kuratsu J, Saitoh Y, Takeshima H, Nishi T and Ushio Y (1996) Expression of tissue factor correlates with grade of malignancy in human glioma. Cancer 77: 1877–1883
Hamuro T, Kamikubo Y, Nakahara Y, Miyamoto S and Funatsu A (1998) Human recombinant tissue factor pathway inhibitor induces apoptosis in cultured human endothelial cells. FEBS Lett 421: 197–202
Kim KJ, Winer J, Armanini M, Gillett N, Phillips HS and Ferrara N (1993) Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumor growth in vivo. Nature (Lond) 362: 841–844
Koomagi R and Volm M (1998) Tissue factor expression in human non-small cell lung carcinoma measured by immunohistochemistry: correlation between tissue factor and angiogenesis. Int J Cancer 79: 19–22
Kumar R, Yoneda J, Bucana C and Fidler IJ (1998) Regulation of distinct steps of angiogenesis by different angiogenic molecules. Int J Oncol 12: 749–757
Millauer B, Schawver LK, Plate KH, Risau W and Ullrich A (1994) Glioblastoma growth inhibited in vivo by a dominant-negative Flk-1 mutant. Nature (Lond) 367: 576–579
Ng SY, Gunning P, Eddy R, Ponte P, Leavitt J, Shows T and Kedes L (1985) Evolution of the functional human β-actin gene and its multipseudogene family: conservation of non-coding regions and chromosomal dispersion of pseudogenes. Mol Cell Biol 5: 2720–2732
Ollivier V, Bentolila S, Chabbat J, Hakim J and de Prost D (1998) Tissue factor-dependent vascular endothelial growth factor production by human fibroblasts in response to activated factor VII. Blood 91: 2698–2703
Ott I, Fischer EG, Miyagi Y, Mueller BM and Ruf W (1998) A role for tissue factor in cell adhesion and migration mediated by interaction with actin-binding protein 280. J Cell Biol 140: 1241–1253
Plate KH, Breier G, Weich HA and Risau W (1992) Vascular endothelial growth factor is a potential tumor angiogenesis factor in human gliomas in vivo. Nature (Lond) 359: 845–888
Potgens AJG, Lubsen NH, van Altena G, Schoenmakers JGG, Ruiter DJ and de Waal RMW (1994) Measurement of tissue factor messenger RNA levels in human endothelial cells by a quantitative RT-PCR assay. Thromb Haemost 71: 208–213
Saitoh Y, Kuratsu J, Takeshima H, Yamamoto S and Ushio Y (1995) Expression of osteopontin in human glioma. Its correlation with the malignancy. Lab Invest 72: 55–63
Scarpati EM, Wen D, Broze GJJ, Miletich JP, Flandermeyer RR, Siegel NR and Sadler JE (1987) Human tissue factor: cDNA sequence and chromosome localization of the gene. Biochemistry 26: 5234–5238
Senger DR (1996) Molecular framework for angiogenesis: a complex web of interactions between extravasated plasma proteins and endothelial cell proteins induced by angiogenic cytokines. Am J Pathol 149: 1–7
Senger DR, Ledbetter SR, Claffey KP, Papadopoulos-Sergiou A, Perruzzi CA and Detmar M (1996) Stimulation of endothelial cell migration by vascular permeability factor/vascular endothelial growth factor through cooperative mechanisms involving the αvβ3 integrin, osteopontin, and thrombin. Am J Pathol 149: 293–305
Shoji M, Hancock WW, Abe K, Micko C, Casper KA, Baine RM, Wilcox JN, Danave I, Dillehay DL, Matthews E, Contrino J, Morrissey JH, Gordon S, Edgington TS, Kudryk B, Kreutzer DL and Rickles FR (1998) Activation of coagulation and angiogenesis in cancer – immunohistochemical localization in situ of clotting proteins and vascular endothelial growth factor in human cancer. Am J Pathol 152: 399–411
Takano S, Gately S, Neville ME, Herblin WF, Gross JL, Engelhard H, Perricone M, Eidsvoog K and Brem S (1994a) Suramin, an anticancer and angiosuppressive agent, inhibits endothelial cell binding of basic fibroblast growth factor, migration, proliferation, and induction of urokinase-type plasminogen activator. Cancer Res 54: 2654–2660
Takano S, Gately S, Engelhard H, Tsanaclis AMC and Brem S (1994 b) Suramin inhibits glioma cell proliferation in vitro and in the brain. J Neuro-Oncol 21: 189–201
Takano S, Gately S, Jiang JB and Brem S (1994 c) A diaminoanthraquinone inhibitor of angiogenesis. J Pharmacol Exp Ther 271: 1027–1033
Takano S, Yoshii Y, Kondo S, Suzuki H, Maruno T, Shirai S and Nose T (1996) Concentration of vascular endothelial growth factor in the serum and tumor tissue of brain tumor patients. Cancer Res 56: 2185–2190
Weindel K, Marme D and Weich HA (1992) AIDS-associated Kaposi’s sarcoma cells in culture express vascular endothelial growth factor. Biochem Biophys Res Commun 183: 1167–1174
Zagzag D (1995) Angiogenic growth factors in neural embryogenesis and neoplasia. Am J Pathol 146: 293–309
Zhang Y, Deng Y, Luther T, Muller MM, Zlegler R, Waldnerr R, Stern DM and Nawroth PP (1994) Tissue factor controls the balance of angiogenic and anti-angiogenic properties of tumor cells in mice. J Clin Invest 94: 1320–1327
Zucker S, Mirza H, Conner CE, Lorenz AE, Drews MH, Bahou WR and Jesty J (1998) Vascular endothelial growth factor induces tissue factor and matrix metalloproteinase production in endothelial cells: conversion of prothrombin to thrombin results in progelatinase A activation and cell proliferation. Int J Cancer 75: 780–786
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Takano, S., Tsuboi, K., Tomono, Y. et al. Tissue factor, osteopontin, αvβ3 integrin expression in microvasculature of gliomas associated with vascular endothelial growth factor expression. Br J Cancer 82, 1967–1973 (2000). https://doi.org/10.1054/bjoc.2000.1150
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DOI: https://doi.org/10.1054/bjoc.2000.1150
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