Linked Life Data

14578463

Source:http://linkedlifedata.com/resource/pubmed/id/14578463

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2003-10-27
pubmed:abstractText
Using gene array technology, we recently observed for the first time an up-regulation of laminin alpha4 chain in human gliomas. The data were validated by semiquantitative reverse transcription-PCR for RNA expression and immunohistochemistry for protein expression. Moreover, increase of the alpha4 chain-containing laminin-8 correlated with poor prognosis for patients with brain gliomas. Therefore, we hypothesized that inhibition of laminin-8 expression by a new generation of highly specific and stable antisense oligonucleotides (Morpholino) against chains of laminin-8 could slow or stop the spread of glioma and its recurrence and thus might be a promising approach for glioma therapy. We next sought to establish an in vitro model to test the feasibility of this approach and to optimize conditions for Morpholino treatment. To develop a model, we used human glioblastoma multiforme cell lines M059K and U-87MG cocultured with normal human brain microvascular endothelial cells (HBMVEC). Using Western blot analysis and immunohistochemistry, we confirmed that antisense treatment effectively blocked laminin-8 protein synthesis. Antisense oligonucleotides against both alpha4 and beta1 chains of laminin-8 were able to block significantly the invasion of cocultures through Matrigel. On average, the invasion was blocked by 62% in cocultures of U-87MG with HBMVEC and by 53% in cocultures of M059K with HBMVEC. The results show that laminin-8 may contribute to glioma progression and recurrence not only as part of the neovascularization process but also by directly increasing the invasive potential of tumor cells.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1535-7163
pubmed:author
pubmed:issnType
Print
pubmed:volume
2
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
985-94
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:14578463-Blotting, Western, pubmed-meshheading:14578463-Cell Line, Tumor, pubmed-meshheading:14578463-Cell Survival, pubmed-meshheading:14578463-Cells, Cultured, pubmed-meshheading:14578463-Coculture Techniques, pubmed-meshheading:14578463-Collagen, pubmed-meshheading:14578463-Disease Progression, pubmed-meshheading:14578463-Drug Combinations, pubmed-meshheading:14578463-Glioma, pubmed-meshheading:14578463-Humans, pubmed-meshheading:14578463-Immunohistochemistry, pubmed-meshheading:14578463-Laminin, pubmed-meshheading:14578463-Microscopy, Fluorescence, pubmed-meshheading:14578463-Neoplasm Invasiveness, pubmed-meshheading:14578463-Oligonucleotide Array Sequence Analysis, pubmed-meshheading:14578463-Oligonucleotides, Antisense, pubmed-meshheading:14578463-Proteoglycans, pubmed-meshheading:14578463-RNA, Messenger, pubmed-meshheading:14578463-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:14578463-Up-Regulation
pubmed:year
2003
pubmed:articleTitle
Antisense inhibition of laminin-8 expression reduces invasion of human gliomas in vitro.
pubmed:affiliation
Maxine Dunitz Neurosurgical Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
pubmed:publicationType
Journal Article, In Vitro, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't