Abstract:
:Angiogenesis, the development of new blood vessels from existing vasculature, is crucial for the development and metastasis of solid tumors. Here, we show for the first time that a 24-amino acid peptide derived from the amino terminus of the alpha chain of human fibrinogen (termed "alphastatin") has potent antiangiogenic properties, inhibiting both the migration and tubule formation of human dermal microvascular endothelial cells in response to vascular endothelial growth factor (VEGF) or basic fibroblast growth factor (bFGF) in vitro. Moreover, alphastatin markedly inhibits the growth of tumors in a syngeneic murine model. Tumors from mice receiving daily injections of alphastatin for 12 days exhibited large areas of intravascular disruption and thrombosis with substantial cellular necrosis. Importantly, alphastatin administration had no detectable effect on vessels in such normal tissues as liver, lungs, and kidney. Taken together, these data indicate that alphastatin is a potent new antiangiogenic agent in vitro and antivascular agent in vivo.
journal_name
Bloodjournal_title
Bloodauthors
Staton CA,Brown NJ,Rodgers GR,Corke KP,Tazzyman S,Underwood JC,Lewis CEdoi
10.1182/blood-2003-07-2192subject
Has Abstractpub_date
2004-01-15 00:00:00pages
601-6issue
2eissn
0006-4971issn
1528-0020pii
2003-07-2192journal_volume
103pub_type
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