Source:http://linkedlifedata.com/resource/pubmed/id/19824060
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
4
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| pubmed:dateCreated |
2009-11-17
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| pubmed:abstractText |
Fibronectin (FN) is an extracellular matrix cell-adhesive glycoprotein. The alternative spliced isoform EDB-FN (extra domain B containing FN) is highly expressed in tumour blood vessels and stroma and represents a candidate for tumour targeting. To investigate the impact of different angiogenic micro-environments on EDB-FN expression, we used a tumour model in which human endometrial adenocarcinoma Tet-FGF2 cells overexpressing fibroblast growth factor-2 (FGF2) driven by the tetracycline-responsive promoter were further transfected with a VEGF antisense cDNA, generating AS-VEGF/Tet-FGF2 cells. In this model, the expression of FGF2 plus VEGF results in fast-growing, highly vascularized Tet-FGF2 tumours. Down-regulation of FGF2 production by tetracycline administration and/or of VEGF production by AS-VEGF transduction inhibited tumour growth and vascularization, with profound changes in tumour micro-environment. Quantitative RT-PCR analysis using human EDB-FN primers shows that subcutaneous grafting in immunodeficient mice is per se sufficient to cause a dramatic up-regulation of EDB-FN expression by these cells, as well as by human oesophageal cancer KYSE 30 cells and renal carcinoma Caki-1 cells. However, in vivo down-regulation of VEGF expression, as occurs in AS-VEGF/Tet-FGF2 tumours, and to a lesser extent of FGF2 expression, as occurs in tetracycline-treated Tet-FGF2 tumour-bearing animals, causes significant inhibition of EDB-FN production in tumour grafts, as shown by immunohistochemistry and quantitative RT-PCR analysis. Accordingly, treatment of Tet-FGF2 tumour-bearing animals with the neutralizing anti-murine VEGF receptor-2 antibody DC101, or of Caki-1 tumour-bearing animals with the anti-VEGF antibody bevacizumab, inhibited EDB-FN expression in tumour grafts. EDB-FN down-regulation was paralleled by a decrease in vascularity, thus confirming EDB-FN as a marker of tumour angiogenesis. These data demonstrate that the angiogenic micro-environment, and in particular the VEGF/VEGFR-2 system, plays a key role in modulating EDB-FN expression by tumour cells in vivo. This may have implications for the design of therapeutic strategies targeting EDB-FN in combination with anti-angiogenic and/or cytotoxic drugs.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Angiogenesis Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Monoclonal,
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Monoclonal, Humanized,
http://linkedlifedata.com/resource/pubmed/chemical/Fibroblast Growth Factor 2,
http://linkedlifedata.com/resource/pubmed/chemical/Fibronectins,
http://linkedlifedata.com/resource/pubmed/chemical/Neoplasm Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Isoforms,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Neoplasm,
http://linkedlifedata.com/resource/pubmed/chemical/VEGFA protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Vascular Endothelial Growth Factor A,
http://linkedlifedata.com/resource/pubmed/chemical/bevacizumab
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| pubmed:status |
MEDLINE
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| pubmed:month |
Dec
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| pubmed:issn |
1096-9896
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| pubmed:author | |
| pubmed:issnType |
Electronic
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| pubmed:volume |
219
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
455-62
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| pubmed:dateRevised |
2011-11-17
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| pubmed:meshHeading |
pubmed-meshheading:19824060-Adenocarcinoma,
pubmed-meshheading:19824060-Angiogenesis Inhibitors,
pubmed-meshheading:19824060-Animals,
pubmed-meshheading:19824060-Antibodies, Monoclonal,
pubmed-meshheading:19824060-Antibodies, Monoclonal, Humanized,
pubmed-meshheading:19824060-Endometrial Neoplasms,
pubmed-meshheading:19824060-Female,
pubmed-meshheading:19824060-Fibroblast Growth Factor 2,
pubmed-meshheading:19824060-Fibronectins,
pubmed-meshheading:19824060-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:19824060-Humans,
pubmed-meshheading:19824060-Kidney Neoplasms,
pubmed-meshheading:19824060-Mice,
pubmed-meshheading:19824060-Mice, Nude,
pubmed-meshheading:19824060-Neoplasm Proteins,
pubmed-meshheading:19824060-Neoplasm Transplantation,
pubmed-meshheading:19824060-Neovascularization, Pathologic,
pubmed-meshheading:19824060-Protein Isoforms,
pubmed-meshheading:19824060-RNA, Messenger,
pubmed-meshheading:19824060-RNA, Neoplasm,
pubmed-meshheading:19824060-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:19824060-Transplantation, Heterologous,
pubmed-meshheading:19824060-Vascular Endothelial Growth Factor A
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| pubmed:year |
2009
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| pubmed:articleTitle |
Impact of VEGF-dependent tumour micro-environment on EDB fibronectin expression by subcutaneous human tumour xenografts in nude mice.
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| pubmed:affiliation |
Department of Biomedical Sciences and Biotechnology, University of Brescia, 25123 Brescia, Italy.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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