Suppression of angiogenesis by lentiviral delivery of PEX, a noncatalytic fragment of matrix metalloproteinase 2.

Content Provider	Semantic Scholar
Author	Pfeifer, Alexander Kessler, T. Woodrow Silletti, Steve A. Cheresh, David A. Verma, Inder M.
Copyright Year	2000
Abstract	Modulation of the balance between pro- and antiangiogenic factors holds great promise for the treatment of a broad spectrum of human disease ranging from ischemic heart disease to cancer. This requires both the identification of angiogenic regulators and their efficient delivery to target organs. Here, we demonstrate the use of a noncatalytic fragment of matrix metalloproteinase 2 (termed PEX) delivered by lentiviral vectors in different angiogenesis models. Transduction of human endothelial cells with PEX virus suppressed endothelial invasion and formation of capillary-like structures without affecting chemotaxis in vitro. Lentiviral delivery of PEX blocked basic fibroblast growth factor-induced matrix metalloproteinase 2 activation and angiogenesis on chicken chorioallantoic membranes. PEX expression also inhibited tumor-induced angiogenesis and tumor growth in a nude mouse model. Thus, our study shows that lentiviral vectors can deliver sufficient quantities of antiangiogenic substances to achieve therapeutic effects in vivo.
Starting Page	806
Ending Page	810
Page Count	5
File Format	PDF HTM / HTML
Alternate Webpage(s)	http://www.pnas.org/content/97/22/12227.full.pdf
PubMed reference number	11035804v1
Volume Number	97
Issue Number	22
Journal	Proceedings of the National Academy of Sciences of the United States of America
Language	English
Access Restriction	Open
Subject Keyword	Angiogenesis Inhibitors Angiogenic Process Chemotaxis Fibroblast Growth Factor 2 Heart Diseases Matrix Metalloproteinases Metalloproteases Mice, Nude Myocardial Ischemia Neoplasms Organ PHEX gene Quantity Tissue membrane chorioallantoic membrane
Content Type	Text
Resource Type	Article