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Antisense inhibition of laminin-8 expression reduces invasion of human gliomas in vitro

Khazenzon, Natalya M; Ljubimov, Alexander V; Lakhter, Alexander J; Fujita, Manabu; Fujiwara, Hironobu; Sekiguchi, Kiyotoshi; Sorokin, Lydia LU ; Petajaniemi, Noora; Virtanen, Ismo and Black, Keith L, et al. (2003) In Molecular Cancer Therapeutics 2(10). p.985-994
Abstract
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... (More)
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. (Less)
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Molecular Cancer Therapeutics
volume
2
issue
10
pages
985 - 994
publisher
American Association for Cancer Research
external identifiers
  • pmid:14578463
  • wos:000186054800006
  • scopus:2442701602
ISSN
1538-8514
language
English
LU publication?
yes
id
1d852edd-0230-4aab-a838-df181f44c821 (old id 297867)
date added to LUP
2007-08-03 12:29:49
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2018-05-29 09:23:19
@article{1d852edd-0230-4aab-a838-df181f44c821,
  abstract     = {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.},
  author       = {Khazenzon, Natalya M and Ljubimov, Alexander V and Lakhter, Alexander J and Fujita, Manabu and Fujiwara, Hironobu and Sekiguchi, Kiyotoshi and Sorokin, Lydia and Petajaniemi, Noora and Virtanen, Ismo and Black, Keith L and Ljubimova, Julia Y},
  issn         = {1538-8514},
  language     = {eng},
  number       = {10},
  pages        = {985--994},
  publisher    = {American Association for Cancer Research},
  series       = {Molecular Cancer Therapeutics},
  title        = {Antisense inhibition of laminin-8 expression reduces invasion of human gliomas in vitro},
  volume       = {2},
  year         = {2003},
}