pubmed-article:20064707 | rdf:type | pubmed:Citation | lld:pubmed |
pubmed-article:20064707 | lifeskim:mentions | umls-concept:C0024299 | lld:lifeskim |
pubmed-article:20064707 | lifeskim:mentions | umls-concept:C0027651 | lld:lifeskim |
pubmed-article:20064707 | lifeskim:mentions | umls-concept:C0078058 | lld:lifeskim |
pubmed-article:20064707 | lifeskim:mentions | umls-concept:C0021467 | lld:lifeskim |
pubmed-article:20064707 | lifeskim:mentions | umls-concept:C0033414 | lld:lifeskim |
pubmed-article:20064707 | lifeskim:mentions | umls-concept:C0018270 | lld:lifeskim |
pubmed-article:20064707 | lifeskim:mentions | umls-concept:C1366753 | lld:lifeskim |
pubmed-article:20064707 | lifeskim:mentions | umls-concept:C1332737 | lld:lifeskim |
pubmed-article:20064707 | lifeskim:mentions | umls-concept:C0597170 | lld:lifeskim |
pubmed-article:20064707 | lifeskim:mentions | umls-concept:C0021469 | lld:lifeskim |
pubmed-article:20064707 | lifeskim:mentions | umls-concept:C1879547 | lld:lifeskim |
pubmed-article:20064707 | lifeskim:mentions | umls-concept:C0441712 | lld:lifeskim |
pubmed-article:20064707 | pubmed:issue | 5 | lld:pubmed |
pubmed-article:20064707 | pubmed:dateCreated | 2010-3-8 | lld:pubmed |
pubmed-article:20064707 | pubmed:abstractText | Increased levels of circulating VEGF-A have been demonstrated in patients with non-Hodgkin lymphoma (NHL) and are associated with progressive disease and poor clinical outcome. We investigated the role of VEGF-A in lymphoma tumour growth on a molecular level in order to identify the mechanism of VEGF-A-promoted tumour growth and to identify the potential targets for therapy. We used a model in which Daudi (human Burkitt lymphoma) tumour cells were transduced with VEGF-A165 or an empty vector (negative control) and subcutaneously injected in NOD/SCID mice. The weight of tumours overexpressing VEGF-A was increased 4-fold compared to that of control tumours (p<0.0001), whereas no in vitro growth advantage was demonstrated upon VEGF-A overexpression. VEGF-A-tumours were associated with increased microvessel densities (p=0.004) and increased tumour cell proliferation (Ki67; p<0.001) compared to control tumours. VEGF-A-tumours were characterised by upregulation of phosphorylated STAT-4 and STAT-6 and downregulation of phospho-p27(KIP1), a crucial cell cycle inhibitor (p<0.05). This was accompanied by increased levels of phosphorylated receptor tyrosine kinases, including EGFR (ErbB-2 and ErbB-4, p<0.05), an upstream regulator of STAT proteins. We demonstrated that various mouse-derived cytokines produced by mouse-derived tumour stromal cells are upregulated in VEGF-A-tumours compared to control tumours (p<0.05). These results indicate an important role for the tumour microenvironment in paracrine promotion of lymphoma tumour growth in response to tumour-derived VEGF-A. In conclusion, lymphoma-derived VEGF-A promoted lymphoma tumour growth in a paracrine loop by activation of tumour stromal cells. Our study reveals VEGF-A and STAT proteins as potential additional targets in the treatment of lymphoma. | lld:pubmed |
pubmed-article:20064707 | pubmed:language | eng | lld:pubmed |
pubmed-article:20064707 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:20064707 | pubmed:citationSubset | IM | lld:pubmed |
pubmed-article:20064707 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:20064707 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:20064707 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:20064707 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:20064707 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:20064707 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:20064707 | pubmed:status | MEDLINE | lld:pubmed |
pubmed-article:20064707 | pubmed:month | Mar | lld:pubmed |
pubmed-article:20064707 | pubmed:issn | 1879-0852 | lld:pubmed |
pubmed-article:20064707 | pubmed:author | pubmed-author:KampsWillem... | lld:pubmed |
pubmed-article:20064707 | pubmed:author | pubmed-author:de... | lld:pubmed |
pubmed-article:20064707 | pubmed:author | pubmed-author:RoordaBerber... | lld:pubmed |
pubmed-article:20064707 | pubmed:author | pubmed-author:Ter ElstArjaA | lld:pubmed |
pubmed-article:20064707 | pubmed:author | pubmed-author:ScherpenFrank... | lld:pubmed |
pubmed-article:20064707 | pubmed:author | pubmed-author:Meeuwsen-de... | lld:pubmed |
pubmed-article:20064707 | pubmed:copyrightInfo | Copyright 2009 Elsevier Ltd. All rights reserved. | lld:pubmed |
pubmed-article:20064707 | pubmed:issnType | Electronic | lld:pubmed |
pubmed-article:20064707 | pubmed:volume | 46 | lld:pubmed |
pubmed-article:20064707 | pubmed:owner | NLM | lld:pubmed |
pubmed-article:20064707 | pubmed:authorsComplete | Y | lld:pubmed |
pubmed-article:20064707 | pubmed:pagination | 974-82 | lld:pubmed |
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pubmed-article:20064707 | pubmed:year | 2010 | lld:pubmed |
pubmed-article:20064707 | pubmed:articleTitle | VEGF-A promotes lymphoma tumour growth by activation of STAT proteins and inhibition of p27(KIP1) via paracrine mechanisms. | lld:pubmed |
pubmed-article:20064707 | pubmed:affiliation | Division of Pediatric Oncology/Hematology, Department of Pediatrics, University Medical Center Groningen, University of Groningen, Hanzeplein 1, P.O. Box 30.001, 9700 RB Groningen, The Netherlands. | lld:pubmed |
pubmed-article:20064707 | pubmed:publicationType | Journal Article | lld:pubmed |