Cancer Research Meeting Calendar  Sign up for Cancer Research eTOC's
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Funahashi, Y.
Right arrow Articles by Wakabayashi, T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Funahashi, Y.
Right arrow Articles by Wakabayashi, T.
[Cancer Research 62, 6116-6123, November 1, 2002]
© 2002 American Association for Cancer Research


Experimental Therapeutics

Sulfonamide Derivative, E7820, Is a Unique Angiogenesis Inhibitor Suppressing an Expression of Integrin {alpha}2 Subunit on Endothelium

Yasuhiro Funahashi1, Naoko Hata Sugi1, Taro Semba, Yuji Yamamoto, Shinichi Hamaoka, Naoko Tsukahara-Tamai, Yoichi Ozawa, Akihiko Tsuruoka, Kazumasa Nara, Keiko Takahashi, Tadashi Okabe, Junichi Kamata, Takashi Owa, Norihiro Ueda, Toru Haneda, Masahiro Yonaga, Kentaro Yoshimatsu and Toshiaki Wakabayashi2

Tsukuba Research Laboratories, Eisai Co., Ltd., Ibaraki, Japan 300-2635

In the process of angiogenesis, endothelial adhesion molecules play a significant role in vascular morphogenesis, in coordination with angiogenic factor signaling. Here we report that a novel angiogenesis inhibitor, E7820 (an aromatic sulfonamide derivative), inhibited in vitro proliferation and tube formation of human umbilical vascular endothelial cell (HUVEC). E7820 decreased integrin {alpha}2, 3, 5, and ß1 in confluent culture of HUVEC, and integrin {alpha}2 was initially suppressed in mRNA level, followed by decrement of integrins {alpha}3, 5, and ß1. The inhibition of integrin {alpha}2 expression in HUVEC showed dose dependence but did not alter the level of CD31. Up-regulation of integrin {alpha}2 by phorbol 12-myristate 13-acetate abrogated the inhibitory effect of E7820 on tube formation within type I collagen gel, whereas addition of antibody against integrin {alpha}2 canceled the phorbol 12-myristate 13-acetate effect. These results suggest that E7820 inhibited tube formation through the suppression of integrin {alpha}2. Oral administration of E7820 remarkably resulted in inhibition of tumor-induced angiogenesis in mouse dorsal air sac model, and tumor growth of human colorectal tumor cell lines (WiDr and LoVo) was inhibited in xenotransplanted model in mice. This is the first time that a small molecule has been shown to modulate integrins, and this finding may provide the basis for a new approach to antiangiogenic therapy through the suppression of integrin {alpha}2 on endothelium.




This article has been cited by other articles:


Home page
Arterioscler. Thromb. Vasc. Bio.Home page
R. Silva, G. D'Amico, K. M. Hodivala-Dilke, and L. E. Reynolds
Integrins: The Keys to Unlocking Angiogenesis
Arterioscler Thromb Vasc Biol, October 1, 2008; 28(10): 1703 - 1713.
[Abstract] [Full Text] [PDF]


Home page
J. Biol. Chem.Home page
B. P. Woodall, A. Nystrom, R. A. Iozzo, J. A. Eble, S. Niland, T. Krieg, B. Eckes, A. Pozzi, and R. V. Iozzo
Integrin {alpha}2 1 Is the Required Receptor for Endorepellin Angiostatic Activity
J. Biol. Chem., January 25, 2008; 283(4): 2335 - 2343.
[Abstract] [Full Text] [PDF]


Home page
EndocrinologyHome page
R. K. Trousdale, S. V. Pollak, J. Klein, L. Lobel, Y. Funahashi, N. Feirt, and J. W. Lustbader
Single-Chain Bifunctional Vascular Endothelial Growth Factor (VEGF)-Follicle-Stimulating Hormone (FSH)-C-Terminal Peptide (CTP) Is Superior to the Combination Therapy of Recombinant VEGF plus FSH-CTP in Stimulating Angiogenesis during Ovarian Folliculogenesis
Endocrinology, March 1, 2007; 148(3): 1296 - 1305.
[Abstract] [Full Text] [PDF]


Home page
J. Nutr.Home page
N. Matsuura, Y. Miyamae, K. Yamane, Y. Nagao, Y. Hamada, N. Kawaguchi, T. Katsuki, K. Hirata, S.-I. Sumi, and H. Ishikawa
Aged Garlic Extract Inhibits Angiogenesis and Proliferation of Colorectal Carcinoma Cells
J. Nutr., March 1, 2006; 136(3): 842S - 846S.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
C.-H. Chung, W.-B. Wu, and T.-F. Huang
Aggretin, a snake venom-derived endothelial integrin {alpha}2{beta}1 agonist, induces angiogenesis via expression of vascular endothelial growth factor
Blood, March 15, 2004; 103(6): 2105 - 2113.
[Abstract] [Full Text] [PDF]


Home page
Clin. Cancer Res.Home page
T. Semba, Y. Funahashi, N. Ono, Y. Yamamoto, N. H. Sugi, M. Asada, K. Yoshimatsu, and T. Wakabayashi
An Angiogenesis Inhibitor E7820 Shows Broad-Spectrum Tumor Growth Inhibition in a Xenograft Model: Possible Value of Integrin {alpha}2 on Platelets as a Biological Marker
Clin. Cancer Res., February 15, 2004; 10(4): 1430 - 1438.
[Abstract] [Full Text] [PDF]


Home page
J. Biol. Chem.Home page
S. M. Sweeney, G. DiLullo, S. J. Slater, J. Martinez, R. V. Iozzo, J. L. Lauer-Fields, G. B. Fields, and J. D. S. Antonio
Angiogenesis in Collagen I Requires {alpha}2{beta}1 Ligation of a GFP*GER Sequence and Possibly p38 MAPK Activation and Focal Adhesion Disassembly
J. Biol. Chem., August 15, 2003; 278(33): 30516 - 30524.
[Abstract] [Full Text] [PDF]




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
Copyright © 2002 by the American Association for Cancer Research.