Linked Life Data

11280779

Source:http://linkedlifedata.com/resource/pubmed/id/11280779

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2001-3-30
pubmed:abstractText
Tumor angiogenesis progresses by a dynamic balance between tumor vascular regression and growth. Angiopoietin (Ang)-2 (the natural antagonist for the angiogenic Tie-2 receptor) and vascular endothelial growth factor (VEGF) are thought to be critical regulators in this process; therefore, these may play a critical role in cancer aggressiveness. The aim of this study was to clarify the clinical and biological significance of the expression of Ang-2 in human gastric cancers and to investigate the relationship between Ang-2 together with VEGF and the induction of proteases such as matrix metalloproteinases (MMPs) in the process of tumor development. Eighty-five individuals with gastric cancer, who had undergone surgery without preoperative treatment, were studied. A stable transfectant of the human MKN-7 gastric cancer cell lines with an Ang-2 expression vector was used for the experimental study. First, we examined the relationship between the mRNA expression of Angs by Northern blot analysis and clinicopathological features. High Ang-2-expression cases showed more frequent vascular involvement and more advanced stages of disease compared with low Ang-2-expression cases (P < 0.05). With regard to prognosis, the survival time for patients in the high-Ang-2 mRNA group was significantly shorter (P < 0.05). When we examined the localization of Ang-2 in human gastric cancers, immunohistochemical analysis revealed that this protein was expressed predominantly in cancer tissues when compared with normal tissues. Interestingly it was expressed not only in endothelia cells (ECs) but also in cancer cells. Second, Ang-2-transfected cells were implanted in vivo into the gastric walls of nude mice. Ang-2-transfectant mice developed highly metastatic tumors with hypervascularity as compared with MKN-7 or control vector-transfectant tumors. There was a significant correlation between Ang-2 mRNA expression and lower grade of vessel maturation. Third, on the basis of the in vivo data, we focused on production of proteases such as MMPs to investigate possible mechanisms in these processes. MMP-1, MMP-9, and urokinase-type plasminogen activator in ECs were strongly up-regulated by Ang-2 in the presence of VEGF in vitro. These data suggest that production of Ang-2 is implicated in tumor development in human gastric cancers. Its production may contribute to tumor angiogenesis by induction of proteases in ECs, which may be enhanced in the presence of VEGF.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
61
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2145-53
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:11280779-Angiopoietin-2, pubmed-meshheading:11280779-Animals, pubmed-meshheading:11280779-Endothelial Growth Factors, pubmed-meshheading:11280779-Endothelium, Vascular, pubmed-meshheading:11280779-Female, pubmed-meshheading:11280779-Humans, pubmed-meshheading:11280779-Immunohistochemistry, pubmed-meshheading:11280779-Lymphokines, pubmed-meshheading:11280779-Male, pubmed-meshheading:11280779-Matrix Metalloproteinases, pubmed-meshheading:11280779-Mice, pubmed-meshheading:11280779-Mice, Inbred BALB C, pubmed-meshheading:11280779-Mice, Nude, pubmed-meshheading:11280779-Neovascularization, Pathologic, pubmed-meshheading:11280779-Protein Biosynthesis, pubmed-meshheading:11280779-Proteins, pubmed-meshheading:11280779-Receptor, TIE-2, pubmed-meshheading:11280779-Receptor Protein-Tyrosine Kinases, pubmed-meshheading:11280779-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:11280779-Stomach Neoplasms, pubmed-meshheading:11280779-Transfection, pubmed-meshheading:11280779-Tumor Cells, Cultured, pubmed-meshheading:11280779-Urokinase-Type Plasminogen Activator, pubmed-meshheading:11280779-Vascular Endothelial Growth Factor A, pubmed-meshheading:11280779-Vascular Endothelial Growth Factors
pubmed:year
2001
pubmed:articleTitle
Angiopoietin-2 is related to tumor angiogenesis in gastric carcinoma: possible in vivo regulation via induction of proteases.
pubmed:affiliation
Department of Surgery, Medical Institute of Bioregulation, Kyushu University, Beppu, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't