June 4, 2013
Genetic Traits Of Cells Responsible For One Type Of Brain Cancer Discovered
redOrbit Staff & Wire Reports — Your Universe Online
The genetic traits of glial cells -- the cells which give rise to the most common form of malignant brain cancer in humans -- have been identified by a team of researchers led by University of Rochester Medical Center (URMC) neurologist Dr. Steven Goldman.“This study identifies a core set of genes and pathways that are dysregulated during both the early and late stages of tumor progression,” Goldman, senior author of the study and the co-director of the URMC Center for Translational Neuromedicine, said in a statement Monday. “By virtue of their marked difference from normal cells, these genes appear to comprise a promising set of targets for therapeutic intervention.”
The brain tumors, which are known as gliomas, arise from those glial cells, which are found in the central nervous system. Gliomas progress in severity over time, the researchers said, and they ultimately turn into glioblastomas — highly invasive tumors that are difficult to treat and are, in most cases, almost always fatal.
Currently, surgery, radiation therapy, and chemotherapy are used to treat the disease, but they can only delay the cancer´s progression and ultimately prove ineffective at combating the tumor. That could change thanks to the new study, which has been published in the journal Cell Reports.
“Cancer research has been transformed over the past several years by new concepts arising from stem cell biology,” URMC explained. “Scientists now appreciate that many cancers are the result of rogue stem cells or their offspring, known as progenitor cells. Traditional cancer therapies often do not prevent a recurrence of the disease since they may not effectively target and destroy the cancer-causing stem cells that lie at the heart of the tumors.”
“Gliomas are one such example,” they added. “The source of the cancer is“¦ the glial progenitor cell. The cells, which arise from and maintain characteristics of stem cells, comprise about three percent of the cell population of the human brain. When these cells become cancerous they are transformed into glioma stem cells, essentially glial progenitor cells whose molecular machinery has gone awry, resulting in uncontrolled cell division.”
Goldman and his colleagues have been studying normal glial progenitor cells for several years. They primarily have focused their efforts on using these cells to treat multiple sclerosis and other neurological disorders. However, during the course of their work, they have gained an enhanced understanding of glial progenitor cell biology, as well as the molecular and genetic changes that transform them into cancers.
The researchers took human tissue samples that represented the three principal stages of the cancer, and were able to both pinpoint and isolate the cancer-inducing stem cells. They then compared the gene expression profiles of these cancer stem cells to those of normal glial progenitor cells. Their goal was to determine the earliest point in which genetic changes associated with cancer formation occurs and identify the genes that were both unique to the cancer-causing stem cells and expressed at every stage of the disease´s progression.
“Out of a pool over 44,000 tested genes and sequences, the scientists identified a small set of genes in the cancerous glioma progenitor cells that were over-expressed at all stages of malignancy,” URMC said. “These genes formed a unique ℠signature´ that identified the tumor progenitor cells and enabled the scientists to define a corresponding set of potential therapeutic targets present throughout all stages of the cancer.”
To test their hypothesis, Goldman and his colleagues targeted one of the genes that was highly overexpressed in the glioma progenitor cells. This gene, which is known as SIX1, is active in the early development in the nervous system but had not previously been detected in the adult brain.
SIX1 signaling had previously been linked to breast and ovarian cancer, which led the researchers to believe that it could also contribute to brain cancer as well. Sure enough, when they blocked the gene´s expression, the cancer cells stopped growing and the implanted tumors actually began to shrink.
“This study gives us a blueprint to develop new therapies,” Goldman said. “We can now devise a strategy to systematically and rationally analyze — and eliminate — glioma stem and progenitor cells using compounds that may selectively target these cells, relative to the normal glial progenitors from which they derive.”
“By targeting genes like SIX1 that are expressed at all stages of glioma progression, we hope to be able to effectively treat gliomas regardless of their stage of malignancy,” he added. “And by targeting the glioma-initiating cells in particular, we hope to lessen the likelihood of recurrence of these tumors, regardless of the stage at which we initiate treatment.”