| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Department of Clinical and Molecular Endocrinology, Tokyo Medical and Dental University Graduate School, Tokyo, Japan
1Correspondence: Department of Clinical and Molecular Endocrinology, Tokyo Medical and Dental University Graduate School, 1–5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan. E-mail: mshichiri.cme{at}tmd.ac.jp
Endostatin is a potent endogenous angiogenesis inhibitor that induces regression of tumors in mice. Neither an extracellular receptor for endostatin nor intracellular signals that result in the regression of tumor vascular beds have been identified. We demonstrate that endostatin, but not angiostatin, at comparable concentrations to those used in in vivo animal trials, rapidly down-regulates many genes in exponentially growing endothelial cells. These include immediate early response genes, cell cycle-related genes, and genes regulating apoptosis inhibitors, mitogen-activated protein kinases, focal adhesion kinase, G-protein-coupled receptors mediating endothelial growth, a mitogenic factor, adhesion molecules, and cell structure components. Suppression of both apoptosis inhibitors and cell proliferation genes may have a limited contribution to the antiangiogenesis process because endostatin induces neither apoptosis nor growth inhibition, unless studied under reduced serum conditions. In contrast, the antimigratory effect of endostatin was rapid and potent even under serum-supplemented conditions. Endostatin caused gene suppression and migration arrest exclusively in endothelial cells, most profoundly in microvascular endothelial cells. The c-myc null fibroblasts obtained by targeted homologous recombination showed an attenuated migration rate compared with isogenic parental cells, whereas the introduction of the c-myc gene into endothelial cells abrogated the antimigratory effect of endostatin. Inhibition of E-box-driven transcription by overexpressing max or mad suppressed endothelial migration. Thus, rapid down-regulation of genes by endostatin neither restores proliferating endothelial cells to their resting states nor induces apoptosis; rather, it potently inhibits endothelial cell migration partly via suppression of c-myc expression.—Shichiri, M., and Hirata, Y. Antiangiogenesis signals by endostatin.
Key Words: endostatin • angiogenesis • angiostatin • migration • c-myc
This article has been cited by other articles:
|
|
 |
|
  S. Yuan, Y. Fu, X. Wang, H. Shi, Y. Huang, X. Song, L. Li, N. Song, and Y. Luo Voltage-dependent anion channel 1 is involved in endostatin-induced endothelial cell apoptosis FASEB J, August 1, 2008; 22(8): 2809 - 2820. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. R. Sodha, M. Boodhwani, R. T. Clements, S.-H. Xu, K. R. Khabbaz, and F. W. Sellke Increased Antiangiogenic Protein Expression in the Skeletal Muscle of Diabetic Swine and Patients Arch Surg, May 1, 2008; 143(5): 463 - 470. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.R. Dass, T.M.N. Tran, and P.F.M. Choong Angiogenesis Inhibitors and the Need for Anti-angiogenic Therapeutics J. Dent. Res., October 1, 2007; 86(10): 927 - 936. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Suhr, K. Brixius, M. de Marees, B. Bolck, H. Kleinoder, S. Achtzehn, W. Bloch, and J. Mester Effects of short-term vibration and hypoxia during high-intensity cycling exercise on circulating levels of angiogenic regulators in humans J Appl Physiol, August 1, 2007; 103(2): 474 - 483. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Schaffhauser, T. Veikkola, K. Strittmatter, H. Antoniadis, K. Alitalo, and G. Christofori Moderate antiangiogenic activity by local, transgenic expression of endostatin in Rip1Tag2 transgenic mice J. Leukoc. Biol., October 1, 2006; 80(4): 669 - 676. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Celik, O. Surucu, C. Dietz, J. V. Heymach, J. Force, I. Hoschele, C. M. Becker, J. Folkman, and O. Kisker Therapeutic Efficacy of Endostatin Exhibits a Biphasic Dose-Response Curve Cancer Res., December 1, 2005; 65(23): 11044 - 11050. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Sugiyama, T. Yoshimoto, K. Tsuchiya, N. Gochou, Y. Hirono, T. Tateno, N. Fukai, M. Shichiri, and Y. Hirata Aldosterone Induces Angiotensin Converting Enzyme Gene Expression via a JAK2-Dependent Pathway in Rat Endothelial Cells Endocrinology, September 1, 2005; 146(9): 3900 - 3906. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Nyberg, L. Xie, and R. Kalluri Endogenous Inhibitors of Angiogenesis Cancer Res., May 15, 2005; 65(10): 3967 - 3979. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. G. Marneros and B. R. Olsen Physiological role of collagen XVIII and endostatin FASEB J, May 1, 2005; 19(7): 716 - 728. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. M. Tjin Tham Sjin, R. Satchi-Fainaro, A. E. Birsner, V.M. S. Ramanujam, J. Folkman, and K. Javaherian A 27-Amino-Acid Synthetic Peptide Corresponding to the NH2-Terminal Zinc-Binding Domain of Endostatin Is Responsible for Its Antitumor Activity Cancer Res., May 1, 2005; 65(9): 3656 - 3663. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Y. Zhang, E. G. Teggatz, A.-P. Zou, W. B. Campbell, and P.-L. Li Endostatin uncouples NO and Ca2+ response to bradykinin through enhanced O2-{middle dot} production in the intact coronary endothelium Am J Physiol Heart Circ Physiol, February 1, 2005; 288(2): H686 - H694. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. K. Skovseth, M. J. T. Veuger, D. R. Sorensen, P. M. De Angelis, and G. Haraldsen Endostatin dramatically inhibits endothelial cell migration, vascular morphogenesis, and perivascular cell recruitment in vivo Blood, February 1, 2005; 105(3): 1044 - 1051. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Fukai, T. Yoshimoto, T. Sugiyama, N. Ozawa, R. Sato, M. Shichiri, and Y. Hirata Concomitant expression of adrenomedullin and its receptor components in rat adipose tissues Am J Physiol Endocrinol Metab, January 1, 2005; 288(1): E56 - E62. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Ozawa, M. Shichiri, N. Fukai, T. Yoshimoto, and Y. Hirata Regulation of Adrenomedullin Gene Transcription and Degradation by the c-myc Gene Endocrinology, September 1, 2004; 145(9): 4244 - 4250. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Yoshimoto, N. Fukai, R. Sato, T. Sugiyama, N. Ozawa, M. Shichiri, and Y. Hirata Antioxidant Effect of Adrenomedullin on Angiotensin II-Induced Reactive Oxygen Species Generation in Vascular Smooth Muscle Cells Endocrinology, July 1, 2004; 145(7): 3331 - 3337. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. W. Davis, Y. Shen, N. A. Mullani, S. Wen, R. S. Herbst, M. O'Reilly, J. L. Abbruzzese, and D. J. McConkey Quantitative Analysis of Biomarkers Defines an Optimal Biological Dose for Recombinant Human Endostatin in Primary Human Tumors Clin. Cancer Res., January 1, 2004; 10(1): 33 - 42. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. R. Macpherson, S. S.W. Ng, S. L. Forbes, G. Melillo, T. Karpova, J. McNally, T. P. Conrads, T. D. Veenstra, A. Martinez, F. Cuttitta, et al. Anti-angiogenic activity of human endostatin is HIF-1-independent in vitro and sensitive to timing of treatment in a human saphenous vein assay Mol. Cancer Ther., September 1, 2003; 2(9): 845 - 854. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. H. DEININGER, W. A. WYBRANIETZ, F. T.C. GRAEPLER, U. M. LAUER, R. MEYERMANN, and H. J. SCHLUESENER Endothelial endostatin release is induced by general cell stress and modulated by the nitric oxide/cGMP pathway FASEB J, July 1, 2003; 17(10): 1267 - 1276. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Nyberg, P. Heikkila, T. Sorsa, J. Luostarinen, R. Heljasvaara, U.-H. Stenman, T. Pihlajaniemi, and T. Salo Endostatin Inhibits Human Tongue Carcinoma Cell Invasion and Intravasation and Blocks the Activation of Matrix Metalloprotease-2, -9, and -13 J. Biol. Chem., June 13, 2003; 278(25): 22404 - 22411. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. C. Murthy, T. J. McFarland, J. Yoken, S. Chen, C. Barone, D. Burke, Y. Zhang, B. Appukuttan, and J. T. Stout Corneal Transduction to Inhibit Angiogenesis and Graft Failure Invest. Ophthalmol. Vis. Sci., May 1, 2003; 44(5): 1837 - 1842. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Matsushita, M. Shichiri, N. Fukai, N. Ozawa, T. Yoshimoto, N. Takasu, and Y. Hirata Urotensin II is an Autocrine/Paracrine Growth Factor for the Porcine Renal Epithelial Cell Line, LLCPK1 Endocrinology, May 1, 2003; 144(5): 1825 - 1831. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Fukai, M. Shichiri, N. Ozawa, M. Matsushita, and Y. Hirata Coexpression of Calcitonin Receptor-Like Receptor and Receptor Activity-Modifying Protein 2 or 3 Mediates the Antimigratory Effect of Adrenomedullin Endocrinology, February 1, 2003; 144(2): 447 - 453. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. P. Thomas, R. Z. Arzoomanian, D. Alberti, R. Marnocha, F. Lee, A. Friedl, K. Tutsch, A. Dresen, P. Geiger, J. Pluda, et al. Phase I Pharmacokinetic and Pharmacodynamic Study of Recombinant Human Endostatin in Patients With Advanced Solid Tumors J. Clin. Oncol., January 15, 2003; 21(2): 223 - 231. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. I. Cline, S. Bicciato, C. DiBello, and M. W. Lingen Prediction of in Vivo Synergistic Activity of Antiangiogenic Compounds by Gene Expression Profiling Cancer Res., December 15, 2002; 62(24): 7143 - 7148. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Ortega and Z. Werb New functional roles for non-collagenous domains of basement membrane collagens J. Cell Sci., November 15, 2002; 115(22): 4201 - 4214. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. S. Herbst, N. A. Mullani, D. W. Davis, K. R. Hess, D. J. McConkey, C. Charnsangavej, M. S. O'Reilly, H.-W. Kim, C. Baker, J. Roach, et al. Development of Biologic Markers of Response and Assessment of Antiangiogenic Activity in a Clinical Trial of Human Recombinant Endostatin J. Clin. Oncol., September 15, 2002; 20(18): 3804 - 3814. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-i. Hanai, J. Gloy, S. A. Karumanchi, S. Kale, J. Tang, G. Hu, B. Chan, R. Ramchandran, V. Jha, V. P. Sukhatme, et al. Endostatin is a potential inhibitor of Wnt signaling J. Cell Biol., August 5, 2002; 158(3): 529 - 539. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Chavakis and S. Dimmeler Regulation of Endothelial Cell Survival and Apoptosis During Angiogenesis Arterioscler. Thromb. Vasc. Biol., June 1, 2002; 22(6): 887 - 893. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-i. Hanai, M. Dhanabal, S. A. Karumanchi, C. Albanese, M. Waterman, B. Chan, R. Ramchandran, R. Pestell, and V. P. Sukhatme Endostatin Causes G1 Arrest of Endothelial Cells through Inhibition of Cyclin D1 J. Biol. Chem., May 3, 2002; 277(19): 16464 - 16469. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Cota-Gomez, N. C. Flores, C. Cruz, A. Casullo, T. Y. Aw, H. Ichikawa, J. Schaack, R. Scheinman, and S. C. Flores The Human Immunodeficiency Virus-1 Tat Protein Activates Human Umbilical Vein Endothelial Cell E-selectin Expression via an NF-kappa B-dependent Mechanism J. Biol. Chem., April 19, 2002; 277(17): 14390 - 14399. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. R. Sorensen, T.-A. Read, T. Porwol, B. R. Olsen, R. Timpl, T. Sasaki, P. O. Iversen, H. B. Benestad, B. K. L. Sim, and R. Bjerkvig Endostatin reduces vascularization, blood flow, and growth in a rat gliosarcoma Neuro-oncol, January 1, 2002; 4(1): 1 - 8. [Abstract] [PDF]
|
|
|
|
|
|
M. Shichiri, K. Yoshinaga, H. Hisatomi, K. Sugihara, and Y. Hirata Genetic and Epigenetic Inactivation of Mitotic Checkpoint Genes hBUB1 and hBUBR1 and Their Relationship to Survival Cancer Res., January 1, 2002; 62(1): 13 - 17. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Mundhenke, J. P. Thomas, G. Wilding, F. T. Lee, F. Kelzc, R. Chappell, R. Neider, L. A. Sebree, and A. Friedl Tissue Examination to Monitor Antiangiogenic Therapy: A Phase I Clinical Trial with Endostatin Clin. Cancer Res., November 1, 2001; 7(11): 3366 - 3374. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
