Linked Life Data

20178102

Source:http://linkedlifedata.com/resource/pubmed/id/20178102

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2010-9-29
pubmed:abstractText
Angiogenesis is crucial for tumor growth and hematogenous metastasis. Specifically expressed and functional protein molecules in angiogenic endothelial cells, especially on the plasma membrane, may be molecular targets for antiangiogenic drugs and drug delivery systems (DDS) in cancer therapy. To discover such target molecules, we performed subcellular proteome analysis of human umbilical vein endothelial cells (HUVECs) treated with or without vascular endothelial growth factor (VEGF) using 2-dimensional difference in-gel electrophoresis (2D-DIGE) and matrix-assisted laser desorption/ionization tandem time-of-flight mass spectrometry (MALDI-TOF/TOF-MS). Among the identified proteins, BiP/GRP78, a molecular chaperone, was highly expressed in the membrane/organelle fraction of HUVECs after VEGF treatment. The involvement of BiP in VEGF-induced angiogenesis was examined by RNA interference. BiP knockdown significantly suppressed VEGF-induced endothelial cell proliferation and VEGF-induced phosphorylation of extracellular-regulated kinase 1/2, phospholipase C-?, and VEGF receptor-2 in HUVECs. Cell surface biotinylation analysis revealed that the cell surface expression of BiP was elevated in VEGF-activated HUVECs. Aiming to apply BiP to a target molecule in liposomal DDS, we developed liposomes modified with the WIFPWIQL peptide, which has been shown to bind to BiP, and investigated its potential for cancer therapy. The WIFPWIQL-modified liposomes (WIFPWIQL liposomes) were significantly taken up by VEGF-activated HUVECs as compared to peptide-unmodified liposomes. WIFPWIQL liposomes appeared to accumulate in tumor endothelial cells in vivo. WIFPWIQL liposomes containing doxorubicin significantly suppressed tumor growth and prolonged the survival of colon26 NL-17 carcinoma cell-bearing mice. In summary, BiP may regulate VEGF-induced endothelial cell proliferation through VEGFR-2-mediated signaling and be an effective target molecule for cancer antineovascular therapy.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1097-0215
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
127
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2685-98
pubmed:meshHeading
pubmed-meshheading:20178102-Angiogenesis Inhibitors, pubmed-meshheading:20178102-Animals, pubmed-meshheading:20178102-Colonic Neoplasms, pubmed-meshheading:20178102-Doxorubicin, pubmed-meshheading:20178102-Drug Delivery Systems, pubmed-meshheading:20178102-Electrophoresis, Gel, Two-Dimensional, pubmed-meshheading:20178102-Endothelial Cells, pubmed-meshheading:20178102-Gene Knockdown Techniques, pubmed-meshheading:20178102-Heat-Shock Proteins, pubmed-meshheading:20178102-Humans, pubmed-meshheading:20178102-Liposomes, pubmed-meshheading:20178102-MAP Kinase Signaling System, pubmed-meshheading:20178102-Male, pubmed-meshheading:20178102-Mice, pubmed-meshheading:20178102-Neovascularization, Pathologic, pubmed-meshheading:20178102-Oligopeptides, pubmed-meshheading:20178102-Prostatic Neoplasms, pubmed-meshheading:20178102-Proteomics, pubmed-meshheading:20178102-Spectrometry, Mass, Matrix-Assisted Laser..., pubmed-meshheading:20178102-Vascular Endothelial Growth Factor A
pubmed:year
2010
pubmed:articleTitle
Cancer antineovascular therapy with liposome drug delivery systems targeted to BiP/GRP78.
pubmed:affiliation
Department of Medical Biochemistry, Graduate School of Pharmaceutical Sciences, University of Shizuoka, Suruga-ku, Shizuoka, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't