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Researchers at Vanderbilt-Ingram Cancer Center uncover clue to explain invasive brain tumors
January 12, 2006Researchers at the Vanderbilt-Ingram Cancer Center have uncovered a clue to explain the invasive nature of an aggressive kind of brain tumor called glioblastoma multiforme, or gliomas, and their findings are published in this week's online edition of the journal Oncogene.
Reid Thompson, M.D., director of Neurosurgical Oncology, and his colleague, Moneeb Ehtesham, M.D., assistant professor of Neurological Surgery and Cancer Biology, found a key receptor plays a role in the spread of this tumor.
"We looked at CXCR4, a molecule which has been shown to play a role in other cancers, and found that the more metastatic aggression relates to this molecule. So, we looked at whether this molecule governed this invasion in gliomas," said Ehtesham.
CXCR4 is a receptor that is found in white blood cells and has been shown to play a key role in regulating the movement of cells in the immune system. Finding something to inhibit CXCR4 could potentially lead to treatment options to prevent cancerous cells from moving to other organs.
In animal models, Thompson and Ehtesham found CXCR4 can, in fact, be linked to cell invasion in glioblastoma. "If we look at a brain cancer model in rodents we can see a difference in CXCR4 expression in invasive and non-invasive cells. We found CXCR4 was expressed in the non-invasive cells, but was much higher in invasive cells, or cells from the core of the tumor and cells that had migrated away," said Ehtesham. Thompson said it was significantly higher, "up to thirty- to fortyfold higher in the invasive cells," he added.
Next, Thompson and Ehtesham looked at CXCR4 more closely, in dish studies. They wanted to determine whether cells that have CXCR4 invade more than cells without the molecule. They induced glioblastoma and forced the cells to migrate, comparing migrating brain tumor cells with the cells at the origin of the cancer. Their findings were consistent with the animal studies - CXCR4 was again much higher in the migrating cancer cells than in the core of the tumor. Only this time, even higher - sixty- to eightyfold higher, according to Ehtesham.
The researchers then shut down the CXCR4 function of the receptor. What they found was puzzling. Shutting down the CXCR4 weakened its ability to migrate, but it didn't stop it altogether, just significantly impaired it. "Cancer is finding a way to move around the brain, said Thompson. "This tells us this receptor plays an important role in mediating cell invasion of gliomas," he added.
Ehtesham said it is one of the contributors, but there are many others. The discovery could help experts target new therapies for the aggressive brain tumors. Several studies are under way to look at targeting molecules to specifically shut down CXCR4 for other cancers, but Thompson said no one has linked its expression to the invasive behavior of brain tumor cells, until now. Ehtesham said they are now looking at a neutralizing antibody that binds to CXCR4 and works by sequestering the invasive molecule, as well as small-interference RNA, which is like silencing it by shutting down the expression of the receptor.
"Now we may have a way of blocking the process that allows cancer to spread in the brain, but we will need to know more than just how to shut down these migratory cells to fight this cancer. This is just another tool in our arsenal,\\\
Vanderbilt University Medical Center
CXCR4 is a receptor that is found in white blood cells and has been shown to play a key role in regulating the movement of cells in the immune system. Finding something to inhibit CXCR4 could potentially lead to treatment options to prevent cancerous cells from moving to other organs.
In animal models, Thompson and Ehtesham found CXCR4 can, in fact, be linked to cell invasion in glioblastoma. "If we look at a brain cancer model in rodents we can see a difference in CXCR4 expression in invasive and non-invasive cells. We found CXCR4 was expressed in the non-invasive cells, but was much higher in invasive cells, or cells from the core of the tumor and cells that had migrated away," said Ehtesham. Thompson said it was significantly higher, "up to thirty- to fortyfold higher in the invasive cells," he added.
Next, Thompson and Ehtesham looked at CXCR4 more closely, in dish studies. They wanted to determine whether cells that have CXCR4 invade more than cells without the molecule. They induced glioblastoma and forced the cells to migrate, comparing migrating brain tumor cells with the cells at the origin of the cancer. Their findings were consistent with the animal studies - CXCR4 was again much higher in the migrating cancer cells than in the core of the tumor. Only this time, even higher - sixty- to eightyfold higher, according to Ehtesham.
The researchers then shut down the CXCR4 function of the receptor. What they found was puzzling. Shutting down the CXCR4 weakened its ability to migrate, but it didn't stop it altogether, just significantly impaired it. "Cancer is finding a way to move around the brain, said Thompson. "This tells us this receptor plays an important role in mediating cell invasion of gliomas," he added.
Ehtesham said it is one of the contributors, but there are many others. The discovery could help experts target new therapies for the aggressive brain tumors. Several studies are under way to look at targeting molecules to specifically shut down CXCR4 for other cancers, but Thompson said no one has linked its expression to the invasive behavior of brain tumor cells, until now. Ehtesham said they are now looking at a neutralizing antibody that binds to CXCR4 and works by sequestering the invasive molecule, as well as small-interference RNA, which is like silencing it by shutting down the expression of the receptor.
"Now we may have a way of blocking the process that allows cancer to spread in the brain, but we will need to know more than just how to shut down these migratory cells to fight this cancer. This is just another tool in our arsenal,\\\
Vanderbilt University Medical Center
Brain Tumor Current Events and Brain Tumor News RSSCancer metabolism discovery uncovers new role of IDH1 gene mutation in brain cancer
Agios Pharmaceuticals today announced that its scientists have established, for the first time, that the mutated IDH1 gene has a novel enzyme activity consistent with a cancer-causing gene, or oncogene.
Barrow study identifies new way to biopsy brain tumors in real time
A new miniature, hand-held microscope may allow more precise removal of brain tumors and an easier recognition of tumor locations during surgery.
Men leave: Separation and divorce far more common when the wife is the patient
A woman is six times more likely to be separated or divorced soon after a diagnosis of cancer or multiple sclerosis than if a man in the relationship is the patient, according to a study that examined the role gender played in so-called "partner abandonment." The study also found that the longer the marriage the more likely it would remain intact.
Childhood cancer survivors less likely to marry, Yale researchers find
Adult survivors of childhood cancer are 20 to 25 percent more likely to never marry compared with siblings and the general population, Yale School of Medicine researchers report in a new study published in Cancer Epidemiology, Biomarkers & Prevention, a journal of the American Association for Cancer Research.
Brain tumors in childhood leave a lasting mark on cognition, life status
Brain tumors in childhood cast a long shadow on survivors. The first study of the lasting impact of these tumors -- the most common solid malignancies in childhood -- shows that survivors have ongoing cognitive problems.
Angiochem crosses BBB, shows safety, efficacy in phase 1/2 brain cancer studies
Angiochem, Inc. a clinical-stage biotechnology company developing drugs that are uniquely capable of crossing the blood-brain barrier to treat brain diseases, announced today that its lead drug candidate, ANG1005, has demonstrated a favorable safety and efficacy profile in more than 100 patients with brain cancer from two separate Phase 1 /2 clinical studies in patients with progressive gliomas, including recurrent glioblastoma, and in patients with progressive brain metastases.
Researchers report benefits of new standard treatment study for rare pediatric brain cancer
A team of researchers led by The University of Texas M. D. Anderson Cancer Center unveiled results today from the largest-ever collaborative study addressing the treatment of a rare pediatric brain tumor.
Unequal access: Hispanic children rarely get top-notch care for brain tumors
Hispanic children diagnosed with brain tumors get high-quality treatment at hospitals that specialize in neurosurgery far less often than other children with the same condition, potentially compromising their immediate prognosis and long-term survival, according to research from Johns Hopkins published in October's Pediatrics.
tudy: The new buzz on detecting tinnitus
It's a ringing, a buzzing, a hissing or a clicking - and the patient is the only one who can hear it. Complicating matters, physicians can rarely pinpoint the source of tinnitus, a chronic ringing of the head or ears that can be as quiet as a whisper or as loud as a jackhammer.
New Approach for the Treatment of Malignant Brain Tumors
Initial chemotherapy alone after surgery is just as successful as initial radiation therapy for patients from whom a very malignant brain tumor (anaplastic glioma) was removed. With this treatment, the patients survive on average > 30 months without a recurrence.
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