Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

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)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; ; and , et al. (More)
; ; ; ; ; ; ; ; ; and (Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
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
additional info
The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Pathology, (Lund) (013030000)
id
1d852edd-0230-4aab-a838-df181f44c821 (old id 297867)
date added to LUP
2016-04-01 12:18:38
date last changed
2025-04-04 14:04:08
@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}},
}