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B Berse, LF Brown, L Van de Water, HF Dvorak and DR Senger
Department of Pathology, Beth Israel Hospital, Boston, Massachusetts.
Vascular permeability factor (VPF), also known as vascular endothelial growth factor (VEGF), increases microvascular permeability and is a specific mitogen for endothelial cells. Expression of VPF/VEGF previously was demonstrated in a variety of tumor cells, in cultures of pituitary-derived cells, and in corpus luteum. Here we present evidence, by Northern analysis and in situ hybridization, that the VPF/VEGF gene is expressed in many adult organs, including lung, kidney, adrenal gland, heart, liver, and stomach mucosa, as well as in elicited peritoneal macrophages. The highest levels of VPF/VEGF transcripts were found in epithelial cells of lung alveoli, renal glomeruli and adrenal cortex, and in cardiac myocytes. The prominence of VPF/VEGF mRNA in these tissues suggests a possible role for VPF/VEGF in regulating baseline microvascular permeability, which is essential for tissue nutrition and waste removal. We also demonstrate particularly high VPF/VEGF mRNA levels in several human tumors, where it may be involved in promoting tumor angiogenesis and stroma generation, both as an endothelial cell mitogen and indirectly by its permeability enhancing effect that leads to the deposition of a provisional fibrin gel matrix.
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W. MATSUYAMA, T. HASHIGUCHI, K. MATSUMURO, F. IWAMI, Y. HIROTSU, M. KAWABATA, K. ARIMURA, and M. OSAME Increased Serum Level of Vascular Endothelial Growth Factor in Pulmonary Tuberculosis Am. J. Respir. Crit. Care Med., September 1, 2000; 162(3): 1120 - 1122. [Abstract] [Full Text]
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T. Etoh, K. Shibuta, G. F. Barnard, S. Kitano, and M. Mori Angiogenin Expression in Human Colorectal Cancer: The Role of Focal Macrophage Infiltration Clin. Cancer Res., September 1, 2000; 6(9): 3545 - 3551. [Abstract] [Full Text]
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S. M. Hall, A. A. Hislop, C. M. Pierce, and S. G. Haworth Prenatal Origins of Human Intrapulmonary Arteries . Formation and Smooth Muscle Maturation Am. J. Respir. Cell Mol. Biol., August 1, 2000; 23(2): 194 - 203. [Abstract] [Full Text]
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P. Koehne, C. Willam, E. Strauss, R. Schindler, K.-U. Eckardt, and C. Buhrer Lack of hypoxic stimulation of VEGF secretion from neutrophils and platelets Am J Physiol Heart Circ Physiol, August 1, 2000; 279(2): H817 - H824. [Abstract] [Full Text] [PDF]
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J. Waltenberger, J. Lange, and A. Kranz Vascular Endothelial Growth Factor-A-Induced Chemotaxis of Monocytes Is Attenuated in Patients With Diabetes Mellitus : A Potential Predictor for the Individual Capacity to Develop Collaterals Circulation, July 11, 2000; 102(2): 185 - 190. [Abstract] [Full Text] [PDF]
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J. Maloney, D. Wang, T. Duncan, N. Voelkel, and S. Ruoss Plasma Vascular Endothelial Growth Factor in Acute Mountain Sickness Chest, July 1, 2000; 118(1): 47 - 52. [Abstract] [Full Text] [PDF]
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D. R. Senger and L. Van De Water VEGF Expression by Epithelial and Stromal Cell Compartments : Resolving a Controversy Am. J. Pathol., July 1, 2000; 157(1): 1 - 3. [Full Text] [PDF]
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J. Kishimoto, R. Ehama, Y. Ge, T. Kobayashi, T. Nishiyama, M. Detmar, and R. E. Burgeson In Vivo Detection of Human Vascular Endothelial Growth Factor Promoter Activity in Transgenic Mouse Skin Am. J. Pathol., July 1, 2000; 157(1): 103 - 110. [Abstract] [Full Text] [PDF]
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K. Inoue, J. W. Slaton, D. W. Davis, D. J. Hicklin, D. J. McConkey, T. Karashima, R. Radinsky, and C. P. N. Dinney Treatment of Human Metastatic Transitional Cell Carcinoma of the Bladder in a Murine Model with the Anti-Vascular Endothelial Growth Factor Receptor Monoclonal Antibody DC101 and Paclitaxel Clin. Cancer Res., July 1, 2000; 6(7): 2635 - 2643. [Abstract] [Full Text]
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K. Tae, A. K. El-Naggar, E. Yoo, L. Feng, J. J. Lee, W. K. Hong, W. N. Hittelman, and D. M. Shin Expression of Vascular Endothelial Growth Factor and Microvessel Density in Head and Neck Tumorigenesis Clin. Cancer Res., July 1, 2000; 6(7): 2821 - 2828. [Abstract] [Full Text]
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K. Inoue, J. W. Slaton, B. Y. Eve, S. J. Kim, P. Perrotte, M. D. Balbay, S. Yano, M. Bar-Eli, R. Radinsky, C. A. Pettaway, et al. Interleukin 8 Expression Regulates Tumorigenicity and Metastases in Androgen-independent Prostate Cancer Clin. Cancer Res., May 1, 2000; 6(5): 2104 - 2119. [Abstract] [Full Text] [PDF]
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J. M. Fredriksson, J. M. Lindquist, G. E. Bronnikov, and J. Nedergaard Norepinephrine Induces Vascular Endothelial Growth Factor Gene Expression in Brown Adipocytes through a beta -Adrenoreceptor/cAMP/Protein Kinase A Pathway Involving Src but Independently of Erk1/2 J. Biol. Chem., April 28, 2000; 275(18): 13802 - 13811. [Abstract] [Full Text] [PDF]
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 G. Stockhammer, W. Poewe, S. Burgstaller, F. Deisenhammer, A. Muigg, S. Kiechl, E. Schmutzhard, H. Maier, S. Felber, P. Schumacher, et al. Vascular endothelial growth factor in CSF: A biological marker for carcinomatous meningitis Neurology, April 25, 2000; 54(8): 1670 - 1676. [Abstract] [Full Text] [PDF]
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 D. Feng, J. A. Nagy, R. A. Brekken, A. Pettersson, E. J. Manseau, K. Pyne, R. Mulligan, P. E. Thorpe, H. F. Dvorak, and A. M. Dvorak Ultrastructural Localization of the Vascular Permeability Factor/Vascular Endothelial Growth Factor (VPF/VEGF) Receptor-2 (FLK-1, KDR) in Normal Mouse Kidney and in the Hyperpermeable Vessels Induced by VPF/VEGF-expressing Tumors and Adenoviral Vectors J. Histochem. Cytochem., April 1, 2000; 48(4): 545 - 556. [Abstract] [Full Text]
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A. Otani, H. Takagi, H. Oh, K. Suzuma, M. Matsumura, E. Ikeda, and Y. Honda Angiotensin II-Stimulated Vascular Endothelial Growth Factor Expression in Bovine Retinal Pericytes Invest. Ophthalmol. Vis. Sci., April 1, 2000; 41(5): 1192 - 1199. [Abstract] [Full Text]
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K. Inoue, J. W. Slaton, S. J. Kim, P. Perrotte, B. Y. Eve, M. Bar-Eli, R. Radinsky, and C. P. N. Dinney Interleukin 8 Expression Regulates Tumorigenicity and Metastasis in Human Bladder Cancer Cancer Res., April 1, 2000; 60(8): 2290 - 2299. [Abstract] [Full Text]
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 L. M. Ellis, Y. Takahashi, W. Liu, and R. M. Shaheen Vascular Endothelial Growth Factor in Human Colon Cancer: Biology and Therapeutic Implications Oncologist, April 1, 2000; 5(90001): 11 - 15. [Abstract] [Full Text]
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 Y. Hojo, U. Ikeda, Y. Zhu, M. Okada, S. Ueno, H. Arakawa, H. Fujikawa, T.-a. Katsuki, and K. Shimada Expression of vascular endothelial growth factor in patients with acute myocardial infarction J. Am. Coll. Cardiol., March 15, 2000; 35(4): 968 - 973. [Abstract] [Full Text] [PDF]
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L.-W. Wu, L. D. Mayo, J. D. Dunbar, K. M. Kessler, O. N. Ozes, R. S. Warren, and D. B. Donner VRAP Is an Adaptor Protein That Binds KDR, a Receptor for Vascular Endothelial Cell Growth Factor J. Biol. Chem., February 25, 2000; 275(9): 6059 - 6062. [Abstract] [Full Text] [PDF]
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L.-W. Wu, L. D. Mayo, J. D. Dunbar, K. M. Kessler, M. R. Baerwald, E. A. Jaffe, D. Wang, R. S. Warren, and D. B. Donner Utilization of Distinct Signaling Pathways by Receptors for Vascular Endothelial Cell Growth Factor and Other Mitogens in the Induction of Endothelial Cell Proliferation J. Biol. Chem., February 18, 2000; 275(7): 5096 - 5103. [Abstract] [Full Text] [PDF]
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Y. Kondo, S. Arii, A. Mori, M. Furutani, T. Chiba, and M. Imamura Enhancement of Angiogenesis, Tumor Growth, and Metastasis by Transfection of Vascular Endothelial Growth Factor into LoVo Human Colon Cancer Cell Line Clin. Cancer Res., February 1, 2000; 6(2): 622 - 630. [Abstract] [Full Text]
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M. P. V. Shekhar, J. Werdell, and L. Tait Interaction with Endothelial Cells Is a Prerequisite for Branching Ductal-Alveolar Morphogenesis and Hyperplasia of Preneoplastic Human Breast Epithelial Cells: Regulation by Estrogen Cancer Res., January 1, 2000; 60(2): 439 - 449. [Abstract] [Full Text]
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 M. Streit, L. Riccardi, P. Velasco, L. F. Brown, T. Hawighorst, P. Bornstein, and M. Detmar Thrombospondin-2: A potent endogenous inhibitor of tumor growth and angiogenesis PNAS, December 21, 1999; 96(26): 14888 - 14893. [Abstract] [Full Text] [PDF]
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P. N. Bernatchez, S. Soker, and M. G. Sirois Vascular Endothelial Growth Factor Effect on Endothelial Cell Proliferation, Migration, and Platelet-activating Factor Synthesis Is Flk-1-dependent J. Biol. Chem., October 22, 1999; 274(43): 31047 - 31054. [Abstract] [Full Text] [PDF]
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J. L. Arbiser, G. Raab, R. M. Rohan, S. Paul, K. Hirschi, E. Flynn, E. R. Price, D. E. Fisher, C. Cohen, and M. Klagsbrun Isolation of Mouse Stromal Cells Associated with a Human Tumor Using Differential Diphtheria Toxin Sensitivity Am. J. Pathol., September 1, 1999; 155(3): 723 - 729. [Abstract] [Full Text] [PDF]
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N. E. Tsopanoglou and M. E. Maragoudakis On the Mechanism of Thrombin-induced Angiogenesis. POTENTIATION OF VASCULAR ENDOTHELIAL GROWTH FACTOR ACTIVITY ON ENDOTHELIAL CELLS BY UP-REGULATION OF ITS RECEPTORS J. Biol. Chem., August 20, 1999; 274(34): 23969 - 23976. [Abstract] [Full Text] [PDF]
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H. Oh, H. Takagi, C. Takagi, K. Suzuma, A. Otani, K. Ishida, M. Matsumura, Y. Ogura, and Y. Honda The Potential Angiogenic Role of Macrophages in the Formation of Choroidal Neovascular Membranes Invest. Ophthalmol. Vis. Sci., August 1, 1999; 40(9): 1891 - 1898. [Abstract] [Full Text] [PDF]
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D R Thickett, L Armstrong, and A B Millar Vascular endothelial growth factor (VEGF) in inflammatory and malignant pleural effusions Thorax, August 1, 1999; 54(8): 707 - 710. [Abstract] [Full Text]
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W. Zheng, M. D. Brown, T. A. Brock, R. J. Bjercke, and R. J. Tomanek Bradycardia-Induced Coronary Angiogenesis Is Dependent on Vascular Endothelial Growth Factor Circ. Res., July 23, 1999; 85(2): 192 - 198. [Abstract] [Full Text] [PDF]
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 M. Sondell, G. Lundborg, and M. Kanje Vascular Endothelial Growth Factor Has Neurotrophic Activity and Stimulates Axonal Outgrowth, Enhancing Cell Survival and Schwann Cell Proliferation in the Peripheral Nervous System J. Neurosci., July 15, 1999; 19(14): 5731 - 5740. [Abstract] [Full Text] [PDF]
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P. LASSUS, A. RISTIMAKI, O. YLIKORKALA, L. VIINIKKA, and S. ANDERSSON Vascular Endothelial Growth Factor in Human Preterm Lung Am. J. Respir. Crit. Care Med., May 1, 1999; 159(5): 1429 - 1433. [Abstract] [Full Text] [PDF]
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