Linked Life Data

12384438

Source:http://linkedlifedata.com/resource/pubmed/id/12384438

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2002-10-17
pubmed:abstractText
Homeostasis of the extracellular matrix is a delicate balance between degradation and remodeling, the balance being maintained by the interaction of activated matrix metalloproteinases (MMPs) and specific tissue inhibitors of matrix metalloproteinases (TIMPs). Up-regulation of MMP activity, favoring proteolytic degradation of the basement membrane and extracellular matrix, has been linked to tumor growth and metastasis, as well as tumor-associated angiogenesis, whereas inhibition of MMP activity appears to restrict these processes. We have used retroviral-mediated gene delivery to effect sustained autocrine expression of TIMP-3 in murine neuroblastoma and melanoma tumor cells in order to further examine the ability of TIMPs to inhibit angiogenesis in vivo. Growth of both histologic types of gene-modified tumor cells in severe combined immunodeficiency (SCID) mice was significantly restricted when compared with controls. Grossly, these tumors were small and had few feeding vessels. Histologic evaluation revealed that although tumors overexpressing TIMP-3 had an increased number of CD31(+) endothelial cells, these endothelial cells had not formed functional tubules, as evidenced by decreased vessel continuity and minimal pericyte recruitment. This effect appears to be mediated, in part, by decreased expression of vascular endothelial (VE)-cadherin by endothelial cells in the presence of TIMP-3 as seen both in an in vitro assay and in TIMP-3-overexpressing tumors. Taken together, these results demonstrate that overexpression of TIMP-3 can inhibit angiogenesis and associated tumor growth, and that the antiangiogenic effects of TIMP-3 appear to be mediated through the inhibition of functional capillary morphogenesis.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0006-4971
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
100
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3361-8
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:12384438-Animals, pubmed-meshheading:12384438-Antigens, CD, pubmed-meshheading:12384438-Antigens, CD31, pubmed-meshheading:12384438-Autocrine Communication, pubmed-meshheading:12384438-Cadherins, pubmed-meshheading:12384438-Capillaries, pubmed-meshheading:12384438-Cell Hypoxia, pubmed-meshheading:12384438-Endothelium, Vascular, pubmed-meshheading:12384438-Gene Expression Regulation, Neoplastic, pubmed-meshheading:12384438-Genes, Reporter, pubmed-meshheading:12384438-Green Fluorescent Proteins, pubmed-meshheading:12384438-Luminescent Proteins, pubmed-meshheading:12384438-Matrix Metalloproteinases, pubmed-meshheading:12384438-Melanoma, Experimental, pubmed-meshheading:12384438-Mice, pubmed-meshheading:12384438-Mice, SCID, pubmed-meshheading:12384438-Microcirculation, pubmed-meshheading:12384438-Morphogenesis, pubmed-meshheading:12384438-Neoplasm Proteins, pubmed-meshheading:12384438-Neovascularization, Pathologic, pubmed-meshheading:12384438-Neuroblastoma, pubmed-meshheading:12384438-Recombinant Fusion Proteins, pubmed-meshheading:12384438-Tissue Inhibitor of Metalloproteinase-3, pubmed-meshheading:12384438-Transfection, pubmed-meshheading:12384438-Tumor Cells, Cultured
pubmed:year
2002
pubmed:articleTitle
Enforced expression of tissue inhibitor of matrix metalloproteinase-3 affects functional capillary morphogenesis and inhibits tumor growth in a murine tumor model.
pubmed:affiliation
Departments of Surgery and Hematology/Oncology, St Jude Children's Research Hospital, 332 S. Lauderdale, Memphis, TN 38105, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't