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ANTISENSE INHIBITION OF LAMININ-8 EXPRESSION TO INHIBIT HUMAN GLIOMAS
ANTISENSE INHIBITION OF LAMININ-8 EXPRESSION TO INHIBIT HUMAN GLIOMAS
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机译:层粘连蛋白8的表达对人胶质瘤的抑制作用
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摘要
Using gene array technology, we observed that an increase of the alpha-4 chain-containing Laminin-8 correlated with poor prognosis for patients with brain gliomas. We established that inhibition of Laminin-8 expression by a new generation of highly specific and stable antisense oligonucleotides (Morpholino(TM)) against chains of Laminin-8 could slow or stop the spread of glioma. This was demonstrated in an in vitro model using human glioblastoma multiforme cell lines M059K and U-87MG co-cultured 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 alpha-4 and beta1 chains of laminin-8 blocked significantly the invasion of co-cultures through Matrigel. The results show that Laminin-8 may not only contribute to glioma progression and recurrence as part of the neovascularization process but also by directly increasing the invasive potential of tumor cells.
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