Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2005-4-18
pubmed:abstractText
Matrix metalloproteinases (MMPs) are endopeptidases that play pivotal roles in promoting tumor disease progression, including tumor angiogenesis. In many solid tumors, MMP expression could be attributed to tumor stromal cells and is partially regulated by tumor-stroma interactions via tumor cell-associated extracellular matrix metalloproteinase inducer (EMMPRIN). The role of EMMPRIN during tumor angiogenesis and growth was explored by modulating EMMPRIN expression and activity using recombinant DNA engineering and neutralizing antibodies. In human breast cancer cells, changes in EMMPRIN expression influenced vascular endothelial growth factor (VEGF) production at both RNA and protein levels. In coculture of tumor cells and fibroblasts mimicking tumor-stroma interactions, VEGF expression was induced in an EMMPRIN- and MMP-dependent fashion, and was further enhanced by overexpressing EMMPRIN. Conversely, VEGF expression was inhibited by suppressing EMMPRIN expression in tumor cells, by neutralizing EMMPRIN activity, or by inhibiting MMPs. In vivo, EMMPRIN overexpression stimulated tumor angiogenesis and growth; both were significantly inhibited by antisense suppression of EMMPRIN. Expression of both human and mouse VEGF and MMP, derived from tumor and host cells, respectively, was regulated by EMMPRIN. These results suggest a novel tumor angiogenesis mechanism in which tumor-associated EMMPRIN functionally mediates tumor-stroma interactions and directly contributes to tumor angiogenesis and growth by stimulating VEGF and MMP expression.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
65
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3193-9
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:15833850-Animals, pubmed-meshheading:15833850-Antigens, CD, pubmed-meshheading:15833850-Antigens, CD147, pubmed-meshheading:15833850-Breast Neoplasms, pubmed-meshheading:15833850-Cell Growth Processes, pubmed-meshheading:15833850-Cell Line, Tumor, pubmed-meshheading:15833850-Cell Movement, pubmed-meshheading:15833850-Coculture Techniques, pubmed-meshheading:15833850-Endothelial Cells, pubmed-meshheading:15833850-Female, pubmed-meshheading:15833850-Fibroblasts, pubmed-meshheading:15833850-Humans, pubmed-meshheading:15833850-Matrix Metalloproteinase 2, pubmed-meshheading:15833850-Matrix Metalloproteinase 9, pubmed-meshheading:15833850-Mice, pubmed-meshheading:15833850-Mice, Nude, pubmed-meshheading:15833850-Neovascularization, Pathologic, pubmed-meshheading:15833850-Transplantation, Heterologous, pubmed-meshheading:15833850-Vascular Endothelial Growth Factor A
pubmed:year
2005
pubmed:articleTitle
Extracellular matrix metalloproteinase inducer stimulates tumor angiogenesis by elevating vascular endothelial cell growth factor and matrix metalloproteinases.
pubmed:affiliation
Oncology Research, Centocor, Inc., Malvern, Pennsylvania, USA.
pubmed:publicationType
Journal Article