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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2010-1-14
pubmed:abstractText
Neuropilin-1 (Nrp1) was recently described as a novel receptor for the pro-angiogenic molecule vascular endothelial growth factor (VEGF), indicating a role in tumor angiogenesis and tumor progression. Recent data confirm this assumption by demonstrating that some tumor and endothelial cells express Nrp1. Therefore, we wanted to investigate the potential role of Nrp1-knockdown on hepatoma and endothelial cell function in vitro and tumor growth in vivo. Nrp1 knockdown in SVEC4 - 10 and Hepa129 cells and its influence on signal transduction (MAPK pP38, pAKT, pERK1 / 2) was analyzed by Western blot. Effects on endothelial tube formation were assayed in an in vitro and in vivo matrigel assay. In vivo, effects of siRNA-Nrp1 were analyzed in a subcutaneous hepatoma model. To verify effects on endothelial and tumor cells in vivo, immunohistochemistry for proliferation, apoptosis and endothelial vessels was performed. LightCycler and Western blot analysis showed efficient inhibition of gene expression in SVEC4 - 10 and Hepa129 cells following siRNA-Nrp1 transfection. Signal transduction pathways were not influenced after siRNA-Nrp1 treatment compared to the controls. Endothelial tube formation was reduced by 59 % and 94 % in vitro and in vivo compared to controls, corresponding to reduced VCAM expression. Subcutaneous tumor growth was not influenced after siRNA treatment. Intratumoral proliferation was not altered after treatment with siRNA-Nrp1, whereas microvessel density and apoptosis were reduced after treatment with siRNA-Nrp1 compared to siRNA-Ctrl. In conclusion, inhibition of Nrp1 expression led to strong anti-endothelial effects, whereas tumor cells and tumor growth were not affected.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1439-7803
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
48
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
21-7
pubmed:meshHeading
pubmed-meshheading:20072992-Angiogenesis Inhibitors, pubmed-meshheading:20072992-Animals, pubmed-meshheading:20072992-Apoptosis, pubmed-meshheading:20072992-Cell Line, Tumor, pubmed-meshheading:20072992-Cell Proliferation, pubmed-meshheading:20072992-Endothelium, Vascular, pubmed-meshheading:20072992-Gene Expression Regulation, pubmed-meshheading:20072992-Gene Knockdown Techniques, pubmed-meshheading:20072992-Humans, pubmed-meshheading:20072992-Liver Neoplasms, Experimental, pubmed-meshheading:20072992-Male, pubmed-meshheading:20072992-Mice, pubmed-meshheading:20072992-Mice, Inbred C3H, pubmed-meshheading:20072992-Microcirculation, pubmed-meshheading:20072992-Neoplasm Transplantation, pubmed-meshheading:20072992-Neuropilin-1, pubmed-meshheading:20072992-RNA, Small Interfering, pubmed-meshheading:20072992-Signal Transduction, pubmed-meshheading:20072992-Transfection, pubmed-meshheading:20072992-Vascular Endothelial Growth Factor A
pubmed:year
2010
pubmed:articleTitle
Inhibition of neuropilin-1 by RNA-interference and its angiostatic potential in the treatment of hepatocellular carcinoma.
pubmed:affiliation
Department of Inner Medicine I, University of Bonn, Medical School, Bonn Germany. esther.raskopf@ukb.uni-bonn.de
pubmed:publicationType
Journal Article