by Bob Shepard
Scientists at the University of Alabama at Birmingham have identified a molecular pathway that seems to contribute to the ability of malignant glioma cells in a brain tumor to spread and invade previously healthy brain tissue. Researchers said the findings, published Sept. 19, 2013, in the journal PLOS ONE, provide new drug-discovery targets to rein in the ability of these cells to move.
Gliomas account for about a third of brain tumors, and survival rates are poor; only about half of the 10,000 Americans diagnosed with malignant glioma survive the first year, and only about one quarter survive for two years.
"Malignant gliomas are notorious, not only because of their resistance to conventional chemotherapy and radiation therapy, but also for their ability to invade the surrounding brain, thus causing neurological impairment and death," said Hassan Fathallah-Shaykh, M.D., Ph.D., associate professor in the UAB Department of Neurology. "Brain invasion, a hallmark of gliomas, also helps glioma cells evade therapeutic strategies."
Fathallah-Shaykh said there is a great deal of interest among scientists in the idea that a low-oxygen environment induces glioma cells to react with aggressive movement, migration and brain invasion. A relatively new cancer strategy to shrink tumors is to cut off the tumor's blood supply – and thus its oxygen source – through the use of anti-angiogenesis drugs. Angiogenesis is the process of making new blood vessels.
"Stop angiogenesis and you shut off a tumor's blood and oxygen supply, denying it the components it needs to grow," said Fathallah-Shaykh. "Drugs that stop angiogenesis are believed to create a kind of killing field. This study identified four glioma cell lines that dramatically increased their motility when subjected to a low-oxygen environment – in effect escaping the killing field to create a new colony elsewhere in the brain."
Fathallah-Shaykh and his team then identified two proteins that form a pathway linking low oxygen, or hypoxia, to increased motility.
"We identified a signaling protein that is activated by hypoxia called Src," said Fathallah-Shaykh. "We also identified a downstream protein called neural Wiskott-Aldrich syndrome protein (N-WASP), which is regulated by Src in the cell lines with increased motility."
The researchers then used protein inhibitors to shut off Src and N-WASP. When either protein was inhibited, low oxygen lost its ability to augment cell movement.
"These findings indicate that Src, N-WASP and the linkage between them – which is something we don't fully understand yet – are key targets for drugs that would interfere with the ability of a cell to move." said Fathallah-Shaykh. "If we can stop them from moving, then techniques such as anti-angiogenesis should be much more effective. Anti-motility drugs could be a key component in treating gliomas in the years to come."
Explore further: New biomarker may help in detecting gliomas
More information: www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0075436
Medical Xpress on facebook
Related Stories
New biomarker may help in detecting gliomas
Jan 16, 2013
Researchers using sophisticated genetic testing techniques have identified a promising new biomarker for diagnosis of glioma—the most common type of malignant brain tumor, reports the January issue of Neurosurgery, official journal of the Congres ...
Research targets way to stop brain tumor cell invasion
Mar 29, 2011
Gliomas are brain invaders. A kind of malignant tumor cell, gliomas branch out like tendrils from a central tumor source, spreading cancer throughout the brain. Traditional therapies, such as cutting out the tumor surgically, ...
A circuitous route to therapy resistance
Jun 26, 2013
Gliomas are malignant brain tumors that arise from glial cells called astrocytes, found in the central nervous system. "In treating malignant gliomas, we currently combine radiotherapy with the anticancer drug temozolomide. ...
Protein that helps tumor blood vessels mature could make cancer drugs more effective
Aug 13, 2012
Since anti-cancer drugs are carried to tumors by the bloodstream, abnormal blood vessel development can hamper delivery. In a paper published Aug. 14 in Cancer Cell, researchers at Sanford-Burnham Medica ...
Protein involved in nerve-cell migration implicated in spread of brain cancer
Aug 07, 2013
The invasion of brain-tumor cells into surrounding tissue requires the same protein molecule that neurons need to migrate into position as they differentiate and mature, according to new research from the University of Illinois ...
Recommended for you
Simple, two-question survery accurately screens cancer patients for depression
19 minutes ago
Cancer patients can be accurately screened for major depression with a simple two-question survey, according to a study presented Sept. 23 at the American Society for Radiation Oncology's 55th Annual Meeting.
Research to change how breast cancer treated
1 hour ago
(Medical Xpress)—Research from the newly formed Cambridge Cancer Centre, a collaboration between the University of Cambridge, Cambridge University Hospitals NHS Foundation Trust, Cancer Research UK and ...
Functional disability high among newly diagnosed older breast cancer patients
9 hours ago
Many older women with newly diagnosed breast cancer have difficulty accomplishing daily tasks, and African-Americans seem to be disproportionately affected. Those are the findings of a new study published early online in ...
Eating, exercises improve diet after pharyngeal cancer Tx
Sep 20, 2013
(HealthDay)—Patients who maintain eating and a regimen of swallowing exercises during treatment for pharyngeal cancers have the highest rate of return to a regular diet following treatment, according to ...
Implications of very low risk prostate cancer assessed
Sep 20, 2013
(HealthDay)—The risk of adverse findings at surgery for men with very low risk (VLR) prostate cancer is significantly lower than for those with low risk (LR), according to research published in the October ...
Elvitegravir fixed combination in HIV: Lesser benefit for treatment-naive patients
Sep 20, 2013
The drug combination of elvitegravir, cobicistat, emtricitabine and tenofovir disoproxil (elvitegravir fixed combination, trade name: Stribild) has been approved in Germany since May 2013 for the treatment of adults infected ...
User comments
© Medical Xpress 2011-2013, Phys.org network
by Bob Shepard
Scientists at the University of Alabama at Birmingham have identified a molecular pathway that seems to contribute to the ability of malignant glioma cells in a brain tumor to spread and invade previously healthy brain tissue. Researchers said the findings, published Sept. 19, 2013, in the journal PLOS ONE, provide new drug-discovery targets to rein in the ability of these cells to move.
Gliomas account for about a third of brain tumors, and survival rates are poor; only about half of the 10,000 Americans diagnosed with malignant glioma survive the first year, and only about one quarter survive for two years.
"Malignant gliomas are notorious, not only because of their resistance to conventional chemotherapy and radiation therapy, but also for their ability to invade the surrounding brain, thus causing neurological impairment and death," said Hassan Fathallah-Shaykh, M.D., Ph.D., associate professor in the UAB Department of Neurology. "Brain invasion, a hallmark of gliomas, also helps glioma cells evade therapeutic strategies."
Fathallah-Shaykh said there is a great deal of interest among scientists in the idea that a low-oxygen environment induces glioma cells to react with aggressive movement, migration and brain invasion. A relatively new cancer strategy to shrink tumors is to cut off the tumor's blood supply – and thus its oxygen source – through the use of anti-angiogenesis drugs. Angiogenesis is the process of making new blood vessels.
"Stop angiogenesis and you shut off a tumor's blood and oxygen supply, denying it the components it needs to grow," said Fathallah-Shaykh. "Drugs that stop angiogenesis are believed to create a kind of killing field. This study identified four glioma cell lines that dramatically increased their motility when subjected to a low-oxygen environment – in effect escaping the killing field to create a new colony elsewhere in the brain."
Fathallah-Shaykh and his team then identified two proteins that form a pathway linking low oxygen, or hypoxia, to increased motility.
"We identified a signaling protein that is activated by hypoxia called Src," said Fathallah-Shaykh. "We also identified a downstream protein called neural Wiskott-Aldrich syndrome protein (N-WASP), which is regulated by Src in the cell lines with increased motility."
The researchers then used protein inhibitors to shut off Src and N-WASP. When either protein was inhibited, low oxygen lost its ability to augment cell movement.
"These findings indicate that Src, N-WASP and the linkage between them – which is something we don't fully understand yet – are key targets for drugs that would interfere with the ability of a cell to move." said Fathallah-Shaykh. "If we can stop them from moving, then techniques such as anti-angiogenesis should be much more effective. Anti-motility drugs could be a key component in treating gliomas in the years to come."
Explore further: New biomarker may help in detecting gliomas
More information: www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0075436
Medical Xpress on facebook
Related Stories
New biomarker may help in detecting gliomas
Jan 16, 2013
Researchers using sophisticated genetic testing techniques have identified a promising new biomarker for diagnosis of glioma—the most common type of malignant brain tumor, reports the January issue of Neurosurgery, official journal of the Congres ...
Research targets way to stop brain tumor cell invasion
Mar 29, 2011
Gliomas are brain invaders. A kind of malignant tumor cell, gliomas branch out like tendrils from a central tumor source, spreading cancer throughout the brain. Traditional therapies, such as cutting out the tumor surgically, ...
A circuitous route to therapy resistance
Jun 26, 2013
Gliomas are malignant brain tumors that arise from glial cells called astrocytes, found in the central nervous system. "In treating malignant gliomas, we currently combine radiotherapy with the anticancer drug temozolomide. ...
Protein that helps tumor blood vessels mature could make cancer drugs more effective
Aug 13, 2012
Since anti-cancer drugs are carried to tumors by the bloodstream, abnormal blood vessel development can hamper delivery. In a paper published Aug. 14 in Cancer Cell, researchers at Sanford-Burnham Medica ...
Protein involved in nerve-cell migration implicated in spread of brain cancer
Aug 07, 2013
The invasion of brain-tumor cells into surrounding tissue requires the same protein molecule that neurons need to migrate into position as they differentiate and mature, according to new research from the University of Illinois ...
Recommended for you
Simple, two-question survery accurately screens cancer patients for depression
19 minutes ago
Cancer patients can be accurately screened for major depression with a simple two-question survey, according to a study presented Sept. 23 at the American Society for Radiation Oncology's 55th Annual Meeting.
Research to change how breast cancer treated
1 hour ago
(Medical Xpress)—Research from the newly formed Cambridge Cancer Centre, a collaboration between the University of Cambridge, Cambridge University Hospitals NHS Foundation Trust, Cancer Research UK and ...
Functional disability high among newly diagnosed older breast cancer patients
9 hours ago
Many older women with newly diagnosed breast cancer have difficulty accomplishing daily tasks, and African-Americans seem to be disproportionately affected. Those are the findings of a new study published early online in ...
Eating, exercises improve diet after pharyngeal cancer Tx
Sep 20, 2013
(HealthDay)—Patients who maintain eating and a regimen of swallowing exercises during treatment for pharyngeal cancers have the highest rate of return to a regular diet following treatment, according to ...
Implications of very low risk prostate cancer assessed
Sep 20, 2013
(HealthDay)—The risk of adverse findings at surgery for men with very low risk (VLR) prostate cancer is significantly lower than for those with low risk (LR), according to research published in the October ...
Elvitegravir fixed combination in HIV: Lesser benefit for treatment-naive patients
Sep 20, 2013
The drug combination of elvitegravir, cobicistat, emtricitabine and tenofovir disoproxil (elvitegravir fixed combination, trade name: Stribild) has been approved in Germany since May 2013 for the treatment of adults infected ...
User comments
© Medical Xpress 2011-2013, Phys.org network
0 comments:
Post a Comment