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In lab studies, blocking expression of gene reduces invasion of deadly brain tumor cells

LOS ANGELES (Oct. 19, 2003) In July 2001, scientists at Cedars-Sinai's Maxine Dunitz Neurosurgical Institute published their findings that one "isoform" or variant of a specific gene was significantly upregulated in high-grade, malignant brain tumors called glioblastoma multiforme (GBM). They theorized that this increased activity might be a critical step in the development, progression and spread of these highly aggressive tumors.

Now, in laboratory experiments designed to mimic the environment of a brain tumor and its abnormal influence on surrounding normal blood vessel cells, the researchers have found that by blocking the expression of this gene, laminin-8, they were able to reduce the tumor's ability to invade neighboring tissue. The new study supports the hypothesis that laminin-8 is involved in the spread of these malignancies, and it reinforces the possibility that a therapy may be developed to arrest the tumors by targeting the gene.

In the original study, published in Cancer Research, the scientists used "gene array" technology to rapidly and efficiently analyze the expression of 11,004 genes in samples of low-grade tumors; high-grade tumors; brain tissue that had been located in close proximity to high-grade tumors; and unrelated normal brain tissue.

Two genes were consistently up-regulated in all high-grade and low-grade gliomas and in tissues adjacent to GBMs, the most aggressive gliomas. One of the genes was already known to be over-expressed in gliomas. The other was the alpha-4 chain of laminin, a gene that influences the thin "basement membrane" that lies beneath the surface layer of blood vessels.

One of the alpha-4 chain-containing laminin isoforms, laminin-9, was expressed mainly in the blood vessel walls of low-grade tumors and normal brain. Laminin-8 was expressed primarily in the vessel walls of the high-grade GBMs and the tissue adjacent to these types of tumors. There were some exceptions. In those cases,
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Contact: Sandra Van
sandy@vancommunications.com
1-800-880-2397
Cedars-Sinai Medical Center
19-Oct-2003


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