Linked Life Data

11803470

Source:http://linkedlifedata.com/resource/pubmed/id/11803470

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2002-1-22
pubmed:abstractText
Angiogenesis is essential for tumor growth and blocking this process might be a valid tool for the control of cancer growth. We showed previously that tumor angiogenesis in integrin alpha1-null mice is reduced compared to that of wild type animals and that over-expression of matrix metalloproteinase 9 (MMP-9) in the alpha1-null and consequent generation of angiostatin (an inhibitor of endothelial cell growth) from circulating plasminogen was implicated in the mechanism of tumor inhibition. Our findings suggested that secretion of excess MMPs generates inhibitors of endothelial cell proliferation, including but not necessarily limited to angiostatin, resulting ultimately in auto-inhibition of angiogenesis. Thus MMP inhibitors used as anti-tumor drugs might in fact cause a paradoxical increase in tumor angiogenesis and tumor growth. In order to determine whether MMP-9 expression was directly involved in the regulation of tumor growth, we specifically inhibited or enhanced MMP-9 synthesis in vitro and in vivo, and subsequently analysed primary endothelial cell proliferation and angiostatin synthesis, as well as tumor vascularization and development. We provide evidence that reduction of plasma levels of MMP-9 in either normal or integrin alpha1-null mice leads to decreased synthesis of angiostatin and consequent increased tumor growth and vascularization. In contrast, specifically enhancing MMP-9 expression in vivo caused a reduction in tumor vascularization. These findings are the opposite to other studies suggesting a pro-tumorigenic role for MMP-9, and may account for some of the recently observed failures of anti MMP therapy in tumor treatment.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0950-9232
pubmed:author
pubmed:issnType
Print
pubmed:day
10
pubmed:volume
21
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
272-81
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:11803470-Angiostatins, pubmed-meshheading:11803470-Animals, pubmed-meshheading:11803470-Antigens, CD, pubmed-meshheading:11803470-Antineoplastic Agents, pubmed-meshheading:11803470-Carcinoma, Renal Cell, pubmed-meshheading:11803470-Cell Division, pubmed-meshheading:11803470-Colonic Neoplasms, pubmed-meshheading:11803470-Doxycycline, pubmed-meshheading:11803470-Endothelium, Vascular, pubmed-meshheading:11803470-Growth Substances, pubmed-meshheading:11803470-Integrin alpha1, pubmed-meshheading:11803470-Kidney Neoplasms, pubmed-meshheading:11803470-Matrix Metalloproteinase 9, pubmed-meshheading:11803470-Mice, pubmed-meshheading:11803470-Mice, Inbred BALB C, pubmed-meshheading:11803470-Mice, Inbred Strains, pubmed-meshheading:11803470-Mice, Knockout, pubmed-meshheading:11803470-Neovascularization, Pathologic, pubmed-meshheading:11803470-Peptide Fragments, pubmed-meshheading:11803470-Plasminogen, pubmed-meshheading:11803470-Tumor Cells, Cultured
pubmed:year
2002
pubmed:articleTitle
Low plasma levels of matrix metalloproteinase 9 permit increased tumor angiogenesis.
pubmed:affiliation
Department of Cell Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California, CA 92037, USA. ambra.pozzi@mcmail.vanderbilt.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't