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Antisense inhibitio...
Antisense inhibition of laminin-8 expression reduces invasion of human gliomas in vitro
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Khazenzon, Natalya M (author)
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Ljubimov, Alexander V (author)
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Lakhter, Alexander J (author)
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Fujita, Manabu (author)
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Fujiwara, Hironobu (author)
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Sekiguchi, Kiyotoshi (author)
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- Sorokin, Lydia (author)
- Lund University,Lunds universitet,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine
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Petajaniemi, Noora (author)
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Virtanen, Ismo (author)
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Black, Keith L (author)
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Ljubimova, Julia Y (author)
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(creator_code:org_t)
- 2003
- 2003
- English.
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In: Molecular Cancer Therapeutics. - 1538-8514. ; 2:10, s. 985-994
- Related links:
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https://lup.lub.lu.s...
Abstract
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
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Khazenzon, Natal ...
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Ljubimov, Alexan ...
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Lakhter, Alexand ...
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Fujita, Manabu
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Fujiwara, Hirono ...
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Sekiguchi, Kiyot ...
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show more...
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Sorokin, Lydia
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Petajaniemi, Noo ...
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Virtanen, Ismo
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Black, Keith L
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Ljubimova, Julia ...
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
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Molecular Cancer ...
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Lund University