Featured Research

from universities, journals, and other organizations

Aggressive brain tumors can originate from a range of nervous system cells

Date:
October 22, 2012
Source:
Salk Institute for Biological Studies
Summary:
Scientists have long believed that glioblastoma multiforme (GBM), the most aggressive type of primary brain tumor, begins in glial cells that make up supportive tissue in the brain or in neural stem cells. However, researchers have now found that the tumors can originate from other types of differentiated cells in the nervous system, including cortical neurons.

The blue, green, red and yellow in this image indicate that these neurons are producing proteins typical of immature nerve cells, evidence that they have reverted to a stem cell-like state. Salk scientists found that mature cortical neurons are capable of reverting to this immature state and developing into an aggressive type of brain tumor that was previously thought to only develop from neural stem cells or glia, another type of cell in the brain.
Credit: Courtesy of Dinorah Friedmann-Morvinski

Scientists have long believed that glioblastoma multiforme (GBM), the most aggressive type of primary brain tumor, begins in glial cells that make up supportive tissue in the brain or in neural stem cells. In a paper published October 17 in Science, however, researchers at the Salk Institute for Biological Studies have found that the tumors can originate from other types of differentiated cells in the nervous system, including cortical neurons.

GBM is one of the most devastating brain tumors that can affect humans. Despite progress in genetic analysis and classification, the prognosis of these tumors remains poor, with most patients dying within one to two years of diagnosis. The Salk researcher's findings offer an explanation for the recurrence of GBM following treatment and suggest potential new targets to treat these deadly brain tumors.

"One of the reasons for the lack of clinical advances in GBMs has been the insufficient understanding of the underlying mechanisms by which these tumors originate and progress," says Inder Verma, a professor in Salk's Laboratory of Genetics and the Irwin and Joan Jacobs Chair in Exemplary Life Science.

To better understand this process, Verma's team harnessed the power of modified viruses, called lentiviruses, to disable powerful tumor suppressor genes that regulate the growth of cells and inhibit the development of tumors. With these tumor suppressors deactivated, cancerous cells are given free rein to grow out of control.

To do that, Verma and his colleagues attached small RNA molecules, known as short hairpin RNAs, to the modified viruses and injected them directly into very few cells in the brains of genetically engineered mice that express an enzyme known as CRE specifically in neurons, astrocytes or neural stem cells. The modified viruses target two genes -- -neurofibromatosis 1 (NF1) and p53 -- -that, when mutated, are implicated in severe gliomas like GBM. Using sophisticated analytical techniques, they discovered that neurons genetically converted by the lentiviruses that also produce green fluorescent protein (GFP) as a marker to track the progression of tumors are capable of forming malignant gliomas.

Because the origin of glioblastomas from neurons has not been previously reported, the Salk scientists provided further evidence that mature neurons can be transformed by these oncogenes by isolating cortical neurons from genetically engineered mice and transducing them with one of the lentiviruses. The neurons that were transplanted back into the mice developed the same tumors as the ones in the laboratory.

"Our findings," says lead author Dinorah Friedmann-Morvinski, a postdoctoral researcher in the Laboratory of Genetics, "suggest that, when two critical genes -- -NF-1 and p53 -- -are disabled, mature, differentiated cells acquire the capacity to reprogram [dedifferentiate] to a neuroprogenitor cell-like state, which can not only maintain their plasticity, but also give rise to the variety of cells observed in malignant gliomas."

If scientists can block the process of dedifferentiation or proliferation of dedifferentiated neuroprogenitor cells, they may be able to stop tumor progression. That's important in an aggressive disease like GBM because of its high rate of recurrence.

"Our results offer an explanation of recurrence of gliomas following treatment," says Verma, "because any tumor cell that is not eradicated can continue to proliferate and induce tumor formation, thereby perpetuating the cycle of continuous cell replication to form malignant gliomas."

The scientists say the tumors in their mouse model are similar to GBMs that affect humans. Because they have the same pathology and characteristic genetic signature, scientists can study potential therapies in mice that should, theoretically, work in humans. While they may not eradicate GBM, these therapies may slow the progression of the disease and improve patients' quality of life.

Other researchers on the study were Eugene Ke, Yasushi Soda, Tomotoshi Marumoto and Oded Singer of the Salk Institute; and Eric Bushong and Mark Ellisman of the University of California, San Diego.

The work was supported by the National Institutes of Health, Ipsen/Biomeasure, the Leona M. and Harry B. Helmsley Charitable Trust, the H.N. and Frances C. Berger Foundation, and the National Center for Research Resources.


Story Source:

The above story is based on materials provided by Salk Institute for Biological Studies. Note: Materials may be edited for content and length.


Journal Reference:

  1. D. Friedmann-Morvinski, E. A. Bushong, E. Ke, Y. Soda, T. Marumoto, O. Singer, M. H. Ellisman, I. M. Verma. Dedifferentiation of Neurons and Astrocytes by Oncogenes Can Induce Gliomas in Mice. Science, 2012; DOI: 10.1126/science.1226929

Cite This Page:

Salk Institute for Biological Studies. "Aggressive brain tumors can originate from a range of nervous system cells." ScienceDaily. ScienceDaily, 22 October 2012. <www.sciencedaily.com/releases/2012/10/121022162341.htm>.
Salk Institute for Biological Studies. (2012, October 22). Aggressive brain tumors can originate from a range of nervous system cells. ScienceDaily. Retrieved September 22, 2014 from www.sciencedaily.com/releases/2012/10/121022162341.htm
Salk Institute for Biological Studies. "Aggressive brain tumors can originate from a range of nervous system cells." ScienceDaily. www.sciencedaily.com/releases/2012/10/121022162341.htm (accessed September 22, 2014).

Share This



More Health & Medicine News

Monday, September 22, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Liberia Pleads for Help to Fight Ebola

Liberia Pleads for Help to Fight Ebola

AP (Sep. 22, 2014) Liberia's finance minister is urging the international community to quickly follow through on pledges of cash to battle Ebola. Bodies are piling up in the capital Monrovia as the nation awaits more help. (Sept. 22) Video provided by AP
Powered by NewsLook.com
Ebola Doctor Says Border Controls Critical

Ebola Doctor Says Border Controls Critical

AP (Sep. 22, 2014) A Florida doctor who helped fight the expanding Ebola outbreak in West Africa says the disease can be stopped, but only if nations quickly step up their response and make border control a priority. (Sept. 22) Video provided by AP
Powered by NewsLook.com
Global Ebola Aid Increasing But Critics Say It's Late

Global Ebola Aid Increasing But Critics Say It's Late

Newsy (Sep. 21, 2014) More than 100 tons of medical supplies were sent to West Africa on Saturday, but aid workers say the global response is still sluggish. Video provided by Newsy
Powered by NewsLook.com
Sierra Leone in Lockdown to Control Ebola

Sierra Leone in Lockdown to Control Ebola

AP (Sep. 21, 2014) Sierra Leone residents remained in lockdown on Saturday as part of a massive effort to confine millions of people to their homes in a bid to stem the biggest Ebola outbreak in history. (Sept. 20) Video provided by AP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins