| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
American Journal of Pathology, Vol 146, 368-378, Copyright © 1995 by American Society for Investigative Pathology
REGULAR ARTICLES |
E Hatva, A Kaipainen, P Mentula, J Jaaskelainen, A Paetau, M Haltia and K Alitalo
Department of Pathology, University of Helsinki, Finland.
Key growth factor-receptor interactions involved in angiogenesis are possible targets for therapy of CNS tumors. Vascular endothelial growth factor (VEGF) is a highly specific endothelial cell mitogen that has been shown to stimulate angiogenesis, a requirement for solid tumor growth. The expression of VEGF, the closely related placental growth factor (PIGF), the newly cloned endothelial high affinity VEGF receptors KDR and FLT1, and the endothelial orphan receptors FLT4 and Tie were analyzed by in situ hybridization in normal human brain tissue and in the following CNS tumors: gliomas, grades II, III, IV; meningiomas, grades I and II; and melanoma metastases to the cerebrum. VEGF mRNA was up-regulated in the majority of low grade tumors studied and was highly expressed in cells of malignant gliomas. Significantly elevated levels of Tie, KDR, and FLT1 mRNAs, but not FLT4 mRNA, were observed in malignant tumor endothelia, as well as in endothelia of tissues directly adjacent to the tumor margin. In comparison, there was little or no receptor expression in normal brain vasculature. Our results are consistent with the hypothesis that these endothelial receptors are induced during tumor progression and may play a role in tumor angiogenesis.
This article has been cited by other articles:
 |
|
 |
|
  M. Benesch, M. Windelberg, W. Sauseng, V. Witt, G. Fleischhack, H. Lackner, H. Gadner, U. Bode, and C. Urban Compassionate use of bevacizumab (Avastin(R)) in children and young adults with refractory or recurrent solid tumors Ann. Onc., April 1, 2008; 19(4): 807 - 813. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. J. Dickinson, B. K. Sturges, R. J. Higgins, B. N. Roberts, C. M. Leutenegger, A. W. Bollen, and R. A. LeCouteur Vascular Endothelial Growth Factor mRNA Expression and Peritumoral Edema in Canine Primary Central Nervous System Tumors Vet. Pathol., March 1, 2008; 45(2): 131 - 139. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Li, D. Edholm, F. Lanner, G. Breier, F. Farnebo, A. Dimberg, and L. Claesson-Welsh Lentiviral Rescue of Vascular Endothelial Growth Factor Receptor-2 Expression in Flk1 / Embryonic Stem Cells Shows Early Priming of Endothelial Precursors Stem Cells, December 1, 2007; 25(12): 2987 - 2995. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Bao, Q. Wu, S. Sathornsumetee, Y. Hao, Z. Li, A. B. Hjelmeland, Q. Shi, R. E. McLendon, D. D. Bigner, and J. N. Rich Stem Cell-like Glioma Cells Promote Tumor Angiogenesis through Vascular Endothelial Growth Factor Cancer Res., August 15, 2006; 66(16): 7843 - 7848. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. N. Rich, S. Sathornsumetee, S. T. Keir, M. W. Kieran, A. Laforme, A. Kaipainen, R. E. McLendon, M. W. Graner, B.K. A. Rasheed, L. Wang, et al. ZD6474, a Novel Tyrosine Kinase Inhibitor of Vascular Endothelial Growth Factor Receptor and Epidermal Growth Factor Receptor, Inhibits Tumor Growth of Multiple Nervous System Tumors Clin. Cancer Res., November 15, 2005; 11(22): 8145 - 8157. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Bhattacharya, S. SenBanerjee, Z. Lin, S. Mir, A. Hamik, P. Wang, P. Mukherjee, D. Mukhopadhyay, and M. K. Jain Inhibition of Vascular Permeability Factor/Vascular Endothelial Growth Factor-mediated Angiogenesis by the Kruppel-like Factor KLF2 J. Biol. Chem., August 12, 2005; 280(32): 28848 - 28851. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Podar and K. C. Anderson The pathophysiologic role of VEGF in hematologic malignancies: therapeutic implications Blood, February 15, 2005; 105(4): 1383 - 1395. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Liu, L. H. Cheung, P. Thorpe, and M. G. Rosenblum Mechanistic studies of a novel human fusion toxin composed of vascular endothelial growth factor (VEGF)121 and the serine protease granzyme B: Directed apoptotic events in vascular endothelial cells Mol. Cancer Ther., October 1, 2003; 2(10): 949 - 959. [Abstract] [Full Text]
|
|
|
|
 |
|
 L. E. Bullard, X. Qi, and J. S. Penn Role for Extracellular Signal-Responsive Kinase-1 and -2 in Retinal Angiogenesis Invest. Ophthalmol. Vis. Sci., April 1, 2003; 44(4): 1722 - 1731. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. K. Nuttall, C. J. Pennington, J. Taplin, A. Wheal, V. W. Yong, P. A. Forsyth, and D. R. Edwards Elevated Membrane-Type Matrix Metalloproteinases in Gliomas Revealed by Profiling Proteases and Inhibitors in Human Cancer Cells Mol. Cancer Res., March 1, 2003; 1(5): 333 - 345. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. ILJIN, T. V. PETROVA, T. VEIKKOLA, V. KUMAR, M. POUTANEN, and K. ALITALO A fluorescent Tie1 reporter allows monitoring of vascular development and endothelial cell isolation from transgenic mouse embryos FASEB J, November 1, 2002; 16(13): 1764 - 1774. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. F. Dvorak Vascular Permeability Factor/Vascular Endothelial Growth Factor: A Critical Cytokine in Tumor Angiogenesis and a Potential Target for Diagnosis and Therapy J. Clin. Oncol., November 1, 2002; 20(21): 4368 - 4380. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Gaspar, S. Thai, C. Voland, A. Dube, T. A. Libermann, M.L. Iruela-Arispe, and P. Oettgen Opposing Functions of the Ets Factors NERF and ELF-1 During Chicken Blood Vessel Development Arterioscler. Thromb. Vasc. Biol., July 1, 2002; 22(7): 1106 - 1112. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. M. Veenendaal, H. Jin, S. Ran, L. Cheung, N. Navone, J. W. Marks, J. Waltenberger, P. Thorpe, and M. G. Rosenblum In vitro and in vivo studies of a VEGF121/rGelonin chimeric fusion toxin targeting the neovasculature of solid tumors PNAS, June 11, 2002; 99(12): 7866 - 7871. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. N. Witmer, J. Dai, H. A. Weich, G. F.J.M. Vrensen, and R. O. Schlingemann Expression of Vascular Endothelial Growth Factor Receptors 1, 2, and 3 in Quiescent Endothelia J. Histochem. Cytochem., June 1, 2002; 50(6): 767 - 778. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Matsumoto and L. Claesson-Welsh VEGF Receptor Signal Transduction Sci. Signal., December 11, 2001; 2001(112): re21 - re21. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Ishihama, M. Ohbayashi, N. Kurosawa, T. Kitsukawa, O. Matsuura, Y. Miyake, and T. Muramatsu Colocalization of Neuropilin-1 and Flk-1 in Retinal Neovascularization in a Mouse Model of Retinopathy Invest. Ophthalmol. Vis. Sci., May 1, 2001; 42(6): 1172 - 1178. [Abstract] [Full Text]
|
|
|
|
|
|
E. Audero, I. Cascone, I. Zanon, S. C. Previtali, R. Piva, D. Schiffer, and F. Bussolino Expression of Angiopoietin-1 in Human Glioblastomas Regulates Tumor-Induced Angiogenesis : In Vivo and In Vitro Studies Arterioscler. Thromb. Vasc. Biol., April 1, 2001; 21(4): 536 - 541. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Paavonen, P. Puolakkainen, L. Jussila, T. Jahkola, and K. Alitalo Vascular Endothelial Growth Factor Receptor-3 in Lymphangiogenesis in Wound Healing Am. J. Pathol., May 1, 2000; 156(5): 1499 - 1504. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Veikkola, M. Karkkainen, L. Claesson-Welsh, and K. Alitalo Regulation of Angiogenesis via Vascular Endothelial Growth Factor Receptors Cancer Res., January 1, 2000; 60(2): 203 - 212. [Full Text]
|
|
|
|
|
|
M. Takahama, M. Tsutsumi, T. Tsujiuchi, K. Nezu, K. Kushibe, S. Taniguchi, Y. Kotake, and Y. Konishi Enhanced Expression of Tie2, Its Ligand Angiopoietin-1, Vascular Endothelial Growth Factor, and CD31 in Human Non-Small Cell Lung Carcinomas Clin. Cancer Res., September 1, 1999; 5(9): 2506 - 2510. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W.-c. Lin, A. F-Y. Li, C.-W. Chi, W.-W. Chung, C. L. Huang, W.-Y. Lui, H.-J. Kung, and C.-W. Wu tie-1 Protein Tyrosine Kinase: A Novel Independent Prognostic Marker for Gastric Cancer Clin. Cancer Res., July 1, 1999; 5(7): 1745 - 1751. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Dube, Y. Akbarali, T. N. Sato, T. A. Libermann, and P. Oettgen Role of the Ets Transcription Factors in the Regulation of the Vascular-Specific Tie2 Gene Circ. Res., May 28, 1999; 84(10): 1177 - 1185. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Yabkowitz, S. Meyer, T. Black, G. Elliott, L. A. Merewether, and H. K. Yamane Inflammatory Cytokines and Vascular Endothelial Growth Factor Stimulate the Release of Soluble Tie Receptor From Human Endothelial Cells Via Metalloprotease Activation Blood, March 15, 1999; 93(6): 1969 - 1979. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-P. Theurillat, J. Hainfellner, A. Maddalena, J. Weissenberger, and A. Aguzzi Early Induction of Angiogenetic Signals in Gliomas of GFAP-v-src Transgenic Mice Am. J. Pathol., February 1, 1999; 154(2): 581 - 590. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Lauren, Y. Gunji, and K. Alitalo Is Angiopoietin-2 Necessary for the Initiation of Tumor Angiogenesis? Am. J. Pathol., November 1, 1998; 153(5): 1333 - 1339. [Full Text] [PDF]
|
|
|
|
|
|
A. Stratmann, W. Risau, and K. H. Plate Cell Type-Specific Expression of Angiopoietin-1 and Angiopoietin-2 Suggests a Role in Glioblastoma Angiogenesis Am. J. Pathol., November 1, 1998; 153(5): 1459 - 1466. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Christou, A. Yoshida, V. Arthur, T. Morita, and S. Kourembanas Increased Vascular Endothelial Growth Factor Production in the Lungs of Rats with Hypoxia-induced Pulmonary Hypertension Am. J. Respir. Cell Mol. Biol., June 1, 1998; 18(6): 768 - 776. [Abstract] [Full Text]
|
|
|
|
 |
|
 O Cleaver and P. Krieg VEGF mediates angioblast migration during development of the dorsal aorta in Xenopus Development, January 10, 1998; 125(19): 3905 - 3914. [Abstract] [PDF]
|
|
|
|
|
|
R. Yabkowitz, S. Meyer, D. Yanagihara, D. Brankow, T. Staley, G. Elliott, S. Hu, and B. Ratzkin Regulation of Tie Receptor Expression on Human Endothelial Cells by Protein Kinase C-Mediated Release of Soluble Tie Blood, July 15, 1997; 90(2): 706 - 715. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. O SCHLINGEMANN and V. W M VAN HINSBERGH Role of vascular permeability factor/vascular endothelial growth factor in eye disease Br. J. Ophthalmol., June 1, 1997; 81(6): 501 - 512. [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Kovacs, K. Ikezaki, K. Samoto, T. Inamura, M. Fukui, T. Kawamata, and S. P. Finklestein VEGF and flt: Expression Time Kinetics in Rat Brain Infarct Stroke, October 1, 1996; 27(10): 1865 - 1873. [Abstract] [Full Text]
|
|
|
|
 |
|
 J. Waltenberger, U. Mayr, S. Pentz, and V. Hombach Functional Upregulation of the Vascular Endothelial Growth Factor Receptor KDR by Hypoxia Circulation, October 1, 1996; 94(7): 1647 - 1654. [Abstract] [Full Text]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
