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J. Biol. Chem., Vol. 275, Issue 41, 32281-32288, October 13, 2000
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From the
Expression of Antisense to Integrin Subunit
3
Inhibits Microvascular Endothelial Cell Capillary Tube Formation in
Fibrin*
§,
Department of Biochemistry and Molecular
Biology, Pennsylvania State University College of Medicine, Hershey,
Pennsylvania 17033 and the ¶ Department of Oral Molecular Biology,
School of Dentistry, Oregon Health Sciences University,
Portland, Oregon 97201
v
3
antagonists are potent angiogenesis inhibitors, and several different
classes of inhibitors have been developed, including monoclonal
antibodies, synthetic peptides, and small organic molecules. However,
each class of inhibitor works by the same principal, by blocking the
binding of ligands to v3. In an effort to
develop an v3 inhibitor that
down-regulates the actual level of v3, we
developed an antisense strategy to inhibit
v3 expression in vitro.
3 antisense expressed in endothelial cells specifically down-regulated v3 and inhibited capillary
tube formation, with the extent of down-regulation correlating with the
extent of tube formation inhibition. This inhibition was
matrix-specific, since tube formation was not inhibited in Matrigel.
These findings support the notion that v3
is required for an essential step of angiogenesis in fibrin, namely
capillary tube formation. These results suggest that pseudogenetic
inhibition of 3 integrins using antisense techniques may
ultimately provide a therapeutic means to inhibit angiogenesis in
vivo.
*
This work was supported by a Student Award from the American
Heart Association, Pennsylvania Affiliate (to S. M. D.), Grant-in-aid S98695P from the American Heart Association, Pennsylvania Affiliate (to
D. H. F.), and NHLBI, National Institutes of Health Grants R29HL53997
and K02HL04215 (to D. H. F.).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed. Tel.:
503-494-8602; Fax: 503-494-8918; E-mail:
farrelld@ohsu.edu.
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