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American Journal of Pathology, Vol 149, 293-305, Copyright © 1996 by American Society for Investigative Pathology
REGULAR ARTICLES |
DR Senger, SR Ledbetter, KP Claffey, A Papadopoulos-Sergiou, CA Peruzzi and M Detmar
Department of Pathology, Beth Israel Hospital, Boston, Massachusetts, USA.
We have identified several mechanisms by which the angiogenic cytokine vascular permeability factor/vascular endothelial growth factor (VPF/VEGF) likely regulates endothelial cells (EC) migration. VPF/VEGF induced dermal microvascular EC expression of mRNAs encoding the alphav and beta3 integrin subunits resulting in increased levels of the alphavbeta3 heterodimer at the cell surface, and VPF/VEGF also induced mRNA encoding osteopontin (OPN), an alphavbeta3 ligand. OPN promoted EC migration in vitro; and VPF/VEGF induction of alphavbeta3 was accompanied by increased EC migration toward OPN. Because thrombin cleavage of OPN results in substantial enhancement of OPN's adhesive properties, and because VPF/VEGF promotes increased microvascular permeability leading to activation of the extrinsic coagulation pathway, we also investigated whether VPF/VEGF facilitates thrombin cleavage of OPN in vivo. Consistent with this hypothesis, co-injection of VPF/VEGF together with OPN resulted in rapid cleavage of OPN by endogenous thrombin. Furthermore, in comparison with native OPN, thrombin-cleaved OPN stimulated a greater rate of EC migration in vitro, which was additive to the increased migration associated with induction of alpha v beta 3. Thus, these data demonstrate cooperative mechanisms for VPF/VEGF regulation of EC migration involving the alphavbeta3 integrin, the alphavbeta3 ligand OPN, and thrombin cleavage of OPN. These findings also illustrate an operational link between VPF/VEGF induction of EC gene expression and VPF/VEGF enhancement of microvascular permeability, suggesting that these distinct biological activities may act accordingly to stimulate EC migration during angiogenesis.
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L. Sun, M. Vitolo, and A. Passaniti Runt-related Gene 2 in Endothelial Cells: Inducible Expression and Specific Regulation of Cell Migration and Invasion Cancer Res., July 1, 2001; 61(13): 4994 - 5001. [Abstract] [Full Text] [PDF]
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 F. Takahashi, K. Takahashi, T. Okazaki, K. Maeda, H. Ienaga, M. Maeda, S. Kon, T. Uede, and Y. Fukuchi Role of Osteopontin in the Pathogenesis of Bleomycin-Induced Pulmonary Fibrosis Am. J. Respir. Cell Mol. Biol., March 1, 2001; 24(3): 264 - 271. [Abstract] [Full Text] [PDF]
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Y. Asou, S. R. Rittling, H. Yoshitake, K. Tsuji, K. Shinomiya, A. Nifuji, D. T. Denhardt, and M. Noda Osteopontin Facilitates Angiogenesis, Accumulation of Osteoclasts, and Resorption in Ectopic Bone Endocrinology, March 1, 2001; 142(3): 1325 - 1332. [Abstract] [Full Text] [PDF]
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S. H. Ali, A. L. O’Donnell, D. Balu, M. B. Pohl, M. J. Seyler, S. Mohamed, S. Mousa, and P. Dandona Estrogen Receptor-{{alpha}} in the Inhibition of Cancer Growth and Angiogenesis Cancer Res., December 1, 2000; 60(24): 7094 - 7098. [Abstract] [Full Text]
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A. Sahni and C. W. Francis Vascular endothelial growth factor binds to fibrinogen and fibrin and stimulates endothelial cell proliferation Blood, December 1, 2000; 96(12): 3772 - 3778. [Abstract] [Full Text] [PDF]
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 S. Fischer, M. Wobben, J. Kleinstuck, D. Renz, and W. Schaper Effect of astroglial cells on hypoxia-induced permeability in PBMEC cells Am J Physiol Cell Physiol, October 1, 2000; 279(4): C935 - C944. [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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 G. A. Johnson, T. E. Spencer, R. C. Burghardt, K. M. Taylor, C. A. Gray, and F. W. Bazer Progesterone Modulation of Osteopontin Gene Expression in the Ovine Uterus Biol Reprod, May 1, 2000; 62(5): 1315 - 1321. [Abstract] [Full Text]
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M. A. Chellaiah, N. Soga, S. Swanson, S. McAllister, U. Alvarez, D. Wang, S. F. Dowdy, and K. A. Hruska Rho-A Is Critical for Osteoclast Podosome Organization, Motility, and Bone Resorption J. Biol. Chem., April 14, 2000; 275(16): 11993 - 12002. [Abstract] [Full Text] [PDF]
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M. Chellaiah, N. Kizer, M. Silva, U. Alvarez, D. Kwiatkowski, and K. A. Hruska Gelsolin Deficiency Blocks Podosome Assembly and Produces Increased Bone Mass and Strength J. Cell Biol., February 21, 2000; 148(4): 665 - 678. [Abstract] [Full Text] [PDF]
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 S. Ashkar, G. F. Weber, V. Panoutsakopoulou, M. E. Sanchirico, M. Jansson, S. Zawaideh, S. R. Rittling, D. T. Denhardt, M. J. Glimcher, and H. Cantor Eta-1 (Osteopontin): An Early Component of Type-1 (Cell-Mediated) Immunity Science, February 4, 2000; 287(5454): 860 - 864. [Abstract] [Full Text]
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S. R. Wedge, D. J. Ogilvie, M. Dukes, J. Kendrew, J. O. Curwen, L. F. Hennequin, A. P. Thomas, E. S. E. Stokes, B. Curry, G. H. P. Richmond, et al. ZD4190: An Orally Active Inhibitor of Vascular Endothelial Growth Factor Signaling with Broad-Spectrum Antitumor Efficacy Cancer Res., February 1, 2000; 60(4): 970 - 975. [Abstract] [Full Text]
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N. Munshi, J. E. Groopman, P. S. Gill, and R. K. Ganju c-Src Mediates Mitogenic Signals and Associates with Cytoskeletal Proteins upon Vascular Endothelial Growth Factor Stimulation in Kaposi's Sarcoma Cells J. Immunol., February 1, 2000; 164(3): 1169 - 1174. [Abstract] [Full Text] [PDF]
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M. Peichev, A. J. Naiyer, D. Pereira, Z. Zhu, W. J. Lane, M. Williams, M. C. Oz, D. J. Hicklin, L. Witte, M. A. S. Moore, et al. Expression of VEGFR-2 and AC133 by circulating human CD34+ cells identifies a population of functional endothelial precursors Blood, February 1, 2000; 95(3): 952 - 958. [Abstract] [Full Text] [PDF]
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B. V. Diaz, M.-C. Lenoir, A. Ladoux, C. Frelin, M. Demarchez, and S. Michel Regulation of Vascular Endothelial Growth Factor Expression in Human Keratinocytes by Retinoids J. Biol. Chem., January 7, 2000; 275(1): 642 - 650. [Abstract] [Full Text] [PDF]
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 J. Sodek, B. Ganss, and M.D. McKee Osteopontin Critical Reviews in Oral Biology & Medicine, January 1, 2000; 11(3): 279 - 303. [Abstract] [Full Text] [PDF]
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G. Montrucchio, E. Lupia, E. Battaglia, L. Del Sorbo, M. Boccellino, L. Biancone, G. Emanuelli, and G. Camussi Platelet-Activating Factor Enhances Vascular Endothelial Growth Factor-Induced Endothelial Cell Motility and Neoangiogenesis in a Murine Matrigel Model Arterioscler Thromb Vasc Biol, January 1, 2000; 20(1): 80 - 88. [Abstract] [Full Text] [PDF]
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M. Detmar, P. Velasco, L. Richard, K. P. Claffey, M. Streit, L. Riccardi, M. Skobe, and L. F. Brown Expression of Vascular Endothelial Growth Factor Induces an Invasive Phenotype in Human Squamous Cell Carcinomas Am. J. Pathol., January 1, 2000; 156(1): 159 - 167. [Abstract] [Full Text] [PDF]
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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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 N. SHIJUBO, T. UEDE, S. KON, M. MAEDA, T. SEGAWA, A. IMADA, M. HIRASAWA, and S. ABE Vascular Endothelial Growth Factor and Osteopontin in Stage I Lung Adenocarcinoma Am. J. Respir. Crit. Care Med., October 1, 1999; 160(4): 1269 - 1273. [Abstract] [Full Text]
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G. A. Johnson, R. C. Burghardt, T. E. Spencer, G. R. Newton, T. L. Ott, and F. W. Bazer Ovine Osteopontin: II. Osteopontin and {alpha}v{beta}3 Integrin Expression in the Uterus and Conceptus During the Periimplantation Period Biol Reprod, October 1, 1999; 61(4): 892 - 899. [Abstract] [Full Text]
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N. Kronemann, A. Bouloumie, S. Bassus, C. M. Kirchmaier, R. Busse, and V. B. Schini-Kerth Aggregating Human Platelets Stimulate Expression of Vascular Endothelial Growth Factor in Cultured Vascular Smooth Muscle Cells Through a Synergistic Effect of Transforming Growth Factor-{beta}1 and Platelet-Derived Growth FactorAB Circulation, August 24, 1999; 100(8): 855 - 860. [Abstract] [Full Text] [PDF]
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J. Luo, G. Paranya, and J. Bischoff Noninflammatory Expression of E-Selectin Is Regulated by Cell Growth Blood, June 1, 1999; 93(11): 3785 - 3791. [Abstract] [Full Text] [PDF]
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A. Solovey, L. Gui, S. Ramakrishnan, M. H. Steinberg, and R. P. Hebbel Sickle Cell Anemia as a Possible State of Enhanced Anti-Apoptotic Tone: Survival Effect of Vascular Endothelial Growth Factor on Circulating and Unanchored Endothelial Cells Blood, June 1, 1999; 93(11): 3824 - 3830. [Abstract] [Full Text] [PDF]
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T. Murohara, B. Witzenbichler, I. Spyridopoulos, T. Asahara, B. Ding, A. Sullivan, D. W. Losordo, and J. M. Isner Role of Endothelial Nitric Oxide Synthase in Endothelial Cell Migration Arterioscler Thromb Vasc Biol, May 1, 1999; 19(5): 1156 - 1161. [Abstract] [Full Text] [PDF]
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S. Fischer, M. Clauss, M. Wiesnet, D. Renz, W. Schaper, and G. F. Karliczek Hypoxia induces permeability in brain microvessel endothelial cells via VEGF and NO Am J Physiol Cell Physiol, April 1, 1999; 276(4): C812 - C820. [Abstract] [Full Text] [PDF]
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M. D. Balbay, C. A. Pettaway, H. Kuniyasu, K. Inoue, E. Ramirez, E. Li, I. J. Fidler, and C. P. N. Dinney Highly Metastatic Human Prostate Cancer Growing within the Prostate of Athymic Mice Overexpresses Vascular Endothelial Growth Factor Clin. Cancer Res., April 1, 1999; 5(4): 783 - 789. [Abstract] [Full Text] [PDF]
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G Collo and M. Pepper Endothelial cell integrin alpha5beta1 expression is modulated by cytokines and during migration in vitro J. Cell Sci., January 2, 1999; 112(4): 569 - 578. [Abstract] [PDF]
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L. Ma, J. Y. C. Chow, and C. H. Cho Cigarette smoking delays ulcer healing: role of constitutive nitric oxide synthase in rat stomach Am J Physiol Gastrointest Liver Physiol, January 1, 1999; 276(1): G238 - G248. [Abstract] [Full Text] [PDF]
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 J. A. Ellison, J. J. Velier, P. Spera, Z. L. Jonak, X. Wang, F. C. Barone, G. Z. Feuerstein, T. Abumiya, and G. J. del Zoppo Osteopontin and its Integrin Receptor {alpha}vß3 Are Upregulated During Formation of the Glial Scar After Focal Stroke • Editorial Comment Stroke, August 1, 1998; 29(8): 1698 - 1707. [Abstract] [Full Text] [PDF]
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I. Baumgartner, A. Pieczek, O. Manor, R. Blair, M. Kearney, K. Walsh, and J. M. Isner Constitutive Expression of phVEGF165 After Intramuscular Gene Transfer Promotes Collateral Vessel Development in Patients With Critical Limb Ischemia Circulation, March 31, 1998; 97(12): 1114 - 1123. [Abstract] [Full Text] [PDF]
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B. P. Eliceiri, R. Klemke, S. Stromblad, and D. A. Cheresh Integrin {alpha}v{beta}3 Requirement for Sustained Mitogen-activated Protein Kinase Activity during Angiogenesis J. Cell Biol., March 9, 1998; 140(5): 1255 - 1263. [Abstract] [Full Text] [PDF]
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