Scientists uncover new target for brain cancer treatment

January 9, 2014

A new study is giving researchers hope that novel targeted therapies can be developed for glioblastoma multiforme (GBM), the most common and most aggressive form of brain cancer, after demonstrating for the first time that a gene known as melanoma differentiation associated gene-9/syntenin (mda-9/syntenin) is a driving force behind the disease's aggressive and invasive nature.

Recently published in the journal Neuro-Oncology, the study led by Virginia Commonwealth University Massey Cancer Center and VCU Institute of Molecular Medicine (VIMM) researchers used cell cultures and animal models to uncover the mechanisms by which mda-9/syntenin causes GBM to grow and invade normal . Additionally, by using publicly available genomic database information (bioinformatics) and analyzing tissue samples from patients with GBM, the researchers found that increased levels of mda-9/syntenin correlated with more advanced tumors and shorter survival. The study's discoveries pinpoint molecular targets that could be used to develop new therapies, and also suggest that the gene could be used to help stage and monitor this aggressive disease.

"Our current study represents a major breakthrough in understanding what drives GBM, and it is a starting point for the development of future therapies," says the study's lead author Paul B. Fisher, M.Ph., Ph.D., Thelma Newmeyer Corman Endowed Chair in Cancer Research and co-leader of the Cancer Molecular Genetics research program at VCU Massey Cancer Center, chairman of the Department of Human and Molecular Genetics at VCU School of Medicine and director of the VIMM. "Because mda-9/syntenin is expressed more in advanced disease, we are also hopeful that we may be able to use the gene to monitor for disease progression and test whether certain therapies are working."

Mda-9/syntenin was originally discovered by Fisher, and through bioinformatics he has found that the gene is overexpressed in a majority of cancers. He and his colleagues also found that mda-9/syntenin interacts with a predicted 151 cancer-related proteins through its PDZ domains, which are chains of amino acids that enable cell signaling by facilitating interactions between proteins.

In GBM, Fisher and his colleagues demonstrated that overexpression of mda-9/syntenin enhanced the cells' ability to invade healthy tissue. In contrast, blocking expression of mda-9/syntenin in animal models reduced invasion, suppressed cell migration and caused tumors to shrink. Additionally, blocking the expression of mda-9/syntenin decreased the production and secretion of interleukin 8 (IL-8) proteins, which are signaling proteins that contribute to tumor growth and progression by promoting and the development of new blood vessels, a process known as angiogenesis.

"We are now focusing on developing small molecules, or drugs, that block the binding of specific cancer-promoting proteins that interact with mda-9/syntenin through its PDZ domains," says Fisher. "If successful, these PDZ-targeted therapies could potentially lead to effective treatments for GBM."

Explore further: Novel gene target shows promise for bladder cancer detection and treatment

More information: The full manuscript of this study is available online at: neuro-oncology.oxfordjournals. … jkey=7bky3mv0fplTyPb

Related Stories

Novel gene target shows promise for bladder cancer detection and treatment

July 24, 2013
Scientists from Virginia Commonwealth University Massey Cancer Center have provided evidence from preclinical experiments that a gene known as melanoma differentiation associated gene-9/syntenin (mda-9/syntenin) could be ...

Research breakthrough could halt melanoma metastasis

November 14, 2012
In laboratory experiments, scientists have eliminated metastasis, the spread of cancer from the original tumor to other parts of the body, in melanoma by inhibiting a protein known as melanoma differentiation associated gene-9 ...

Scientists discover how deadly skin cancer spreads into other parts of the body

January 3, 2013
After recently announcing success in eliminating melanoma metastasis in laboratory experiments, scientists at Virginia Commonwealth University Massey Cancer Center have made another important discovery in understanding the ...

Researchers hope newly discovered gene interaction could lead to novel cancer therapies

December 13, 2013
Scientists from Virginia Commonwealth University Massey Cancer Center have revealed how two genes interact to kill a wide range of cancer cells. Originally discovered by the study's lead investigator Paul B. Fisher, M.Ph., ...

Targeted viral therapy destroys breast cancer stem cells in preclinical experiments

June 24, 2013
A promising new treatment for breast cancer being developed at Virginia Commonwealth University Massey Cancer Center and the VCU Institute of Molecular Medicine (VIMM) has been shown in cell culture and in animal models to ...

Recommended for you

No dye: Cancer patients' gray hair darkened on immune drugs

July 21, 2017
Cancer patients' gray hair unexpectedly turned youthfully dark while taking novel drugs, and it has doctors scratching their heads.

Shooting the achilles heel of nervous system cancers

July 20, 2017
Virtually all cancer treatments used today also damage normal cells, causing the toxic side effects associated with cancer treatment. A cooperative research team led by researchers at Dartmouth's Norris Cotton Cancer Center ...

Molecular changes with age in normal breast tissue are linked to cancer-related changes

July 20, 2017
Several known factors are associated with a higher risk of breast cancer including increasing age, being overweight after menopause, alcohol intake, and family history. However, the underlying biologic mechanisms through ...

Immune-cell numbers predict response to combination immunotherapy in melanoma

July 20, 2017
Whether a melanoma patient will better respond to a single immunotherapy drug or two in combination depends on the abundance of certain white blood cells within their tumors, according to a new study conducted by UC San Francisco ...

Discovery could lead to better results for patients undergoing radiation

July 19, 2017
More than half of cancer patients undergo radiotherapy, in which high doses of radiation are aimed at diseased tissue to kill cancer cells. But due to a phenomenon known as radiation-induced bystander effect (RIBE), in which ...

Definitive genomic study reveals alterations driving most medulloblastoma brain tumors

July 19, 2017
The most comprehensive analysis yet of medulloblastoma has identified genomic changes responsible for more than 75 percent of the brain tumors, including two new suspected cancer genes that were found exclusively in the least ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.