Linked Life Data

20679340

Source:http://linkedlifedata.com/resource/pubmed/id/20679340

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
42
pubmed:dateCreated
2010-10-11
pubmed:abstractText
The highly expressed Id1 (inhibitor of DNA binding/differentiation) protein promotes angiogenesis in HCC and is a well established target for anti-angiogenesis therapeutic strategies. Heparan sulfate (HS) mimetics such as PI-88 can abrogate HS-protein interactions to inhibit angiogenesis. Id1 is the direct downstream effector of bone morphogenetic proteins (BMPs), which are angiogenic and HS-binding proteins. Thus, targeting BMPs by HS mimetics may inhibit angiogenesis via attenuating Id1 expression. We report here that a HS mimetic WSS25 potently inhibited the tube formation of HMEC-1 cells on Matrigel and their migration. Meanwhile, WSS25 (25 ?g/ml) nearly completely blocked Id1 expression in the HMEC-1 cells as demonstrated by oligo-angiogenesis microarray analysis and further confirmed by RT-PCR and Western blotting. BMP/Smad/Id1 signaling also was blocked by WSS25 treatment in HMEC-1 cells. Importantly, Id1 knockdown in HMEC-1 cells caused the disruption of their tube formation on Matrigel. By employing quartz crystal microbalance analysis, we found that WSS25 strongly bound to BMP2. Moreover, WSS25 impaired BMP2-induced tube formation of HMEC-1 cells on Matrigel and angiogenesis in Matrigel transplanted into C57BL6 mice. Furthermore, WSS25 (100 mg/kg) abrogated the growth of HCC cells xenografted in male nude mice. Immunohistochemical analysis showed that both the expression of Id1 and the endothelial cell marker CD31 were lower in the WSS25-treated tumor tissue than in the control. Therefore, WSS25 is a potential drug candidate for HCC therapy as a tumor angiogenesis inhibitor.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1083-351X
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
285
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
32638-46
pubmed:dateRevised
2011-10-17
pubmed:meshHeading
pubmed-meshheading:20679340-Animals, pubmed-meshheading:20679340-Bone Morphogenetic Proteins, pubmed-meshheading:20679340-Carcinoma, Hepatocellular, pubmed-meshheading:20679340-Cell Line, Tumor, pubmed-meshheading:20679340-Glucans, pubmed-meshheading:20679340-Heparitin Sulfate, pubmed-meshheading:20679340-Humans, pubmed-meshheading:20679340-Inhibitor of Differentiation Protein 1, pubmed-meshheading:20679340-Liver Neoplasms, pubmed-meshheading:20679340-Male, pubmed-meshheading:20679340-Mice, pubmed-meshheading:20679340-Mice, Inbred BALB C, pubmed-meshheading:20679340-Mice, Inbred C57BL, pubmed-meshheading:20679340-Mice, Nude, pubmed-meshheading:20679340-Molecular Structure, pubmed-meshheading:20679340-Neoplasm Transplantation, pubmed-meshheading:20679340-Neoplasms, Experimental, pubmed-meshheading:20679340-Neovascularization, Pathologic, pubmed-meshheading:20679340-Quartz Crystal Microbalance Techniques, pubmed-meshheading:20679340-Signal Transduction, pubmed-meshheading:20679340-Smad Proteins, pubmed-meshheading:20679340-Transplantation, Heterologous
pubmed:year
2010
pubmed:articleTitle
WSS25 inhibits growth of xenografted hepatocellular cancer cells in nude mice by disrupting angiogenesis via blocking bone morphogenetic protein (BMP)/Smad/Id1 signaling.
pubmed:affiliation
Glycochemistry & Glycobiology Lab, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't