Featured Research

from universities, journals, and other organizations

Vascular Niche Nurtures Brain Tumor Stem Cells

Date:
January 19, 2007
Source:
St. Jude Children's Research Hospital
Summary:
Brain tumors appear to arise from cancer stem cells (CSCs) that live within microscopic protective "niches" formed by blood vessels in the brain; and disrupting these niches is a promising strategy for eliminating the tumors and preventing them from re-growing, according to results of a study by investigators at St. Jude Children's Research Hospital. CSCs are cells that continually multiply, acting as the source of tumors.

Brain tumors appear to arise from cancer stem cells (CSCs) that live within microscopic protective "niches" formed by blood vessels in the brain; and disrupting these niches is a promising strategy for eliminating the tumors and preventing them from re-growing, according to results of a study by investigators at St. Jude Children's Research Hospital. CSCs are cells that continually multiply, acting as the source of tumors.

"The finding that brain CSCs exist in protective vascular (blood vessel) niches helps explain the origin of brain tumors and suggests a new strategy for eliminating them," said Richard Gilbertson, M.D., Ph.D., co-director of the Neurobiology and Brain Tumor Program at St. Jude. Gilbertson is senior author of a report on this work that appears in the January issue of Cancer Cell.

"Our data indicate that brain CSCs are nurtured by these vascular niches and that disrupting them blocks tumor growth by removing CSCs from tumors," he said. "These niches might also protect CSCs from chemotherapy drugs and irradiation therapy. So our findings could explain why aggressive tumors rapidly produce new blood vessels and why brain tumors reappear following treatment."

The St. Jude team first determined that CSCs are located in vascular niches by identifying cells carrying a protein called Nestin that marks stem cells (Nestin+ cells) in four types of brain cancer removed from patients: medulloblastoma, ependymoma, oligodendroglioma and glioblastoma. They found that tumors with the densest system of tiny blood vessels contained the greatest number of Nestin+ cells, and that Nestin+ cells are located next to blood vessels in brain tumors.

The investigators then examined thin sections of brain tumors and found that more than one-third of the Nestin+ cells next to blood vessels in the vascular niches had a mutation known to be linked to cancer, which suggested they were CSCs, Gilbertson said. About 30 percent of these cells were multiplying abnormally and rapidly, as expected for cancer cells.

The team showed in mouse models that CSCs from brain tumors have a more natural tendency to associate closely with blood vessels than do non-CSC tumor cells. The researchers also demonstrated in test tube experiments that CSCs bind closely to cells isolated from human blood vessels. Further, the investigators found that human blood vessel cells release molecules that trigger brain CSCs to keep their identity as stem cells and continue to multiply rapidly.

"This is strong evidence that the cells making up the vascular niche send signals to CSCs in the brain, causing them to grow and multiply," Gilbertson said.

Gilbertson's team also studied the interaction of blood vessel cells with CSCs using mouse models of brain cancer. Mixing brain CSCs with human blood vessel cells dramatically increased the formation and growth of tumors. Brain CSCs inserted into the brain without human blood vessel cells produced tumors slowly, reaching a maximum size after seven weeks. In contrast, tumors formed by mixtures of brain CSCs and blood vessel cells grew much more rapidly, reaching a maximum growth after only four weeks. The blood vessel cells did not increase tumor growth by forming new vessels, but by associating with CSCs and stimulating these directly to produce tumors.

Finally, the investigators showed that increasing the numbers of blood vessels in mouse models of brain tumors markedly increased the numbers of CSCs in tumors. The scientists also showed that drugs that deplete blood vessels from tumors inhibit tumor growth by reducing the number of CSCs. For example, the team depleted blood vessels in tumors with Avastinฎ (bevacizumab), an anti-angiogenic drug that blocks a protein called VEGF. Anti-angiogenic drugs block the formation of new blood vessels.

"This strongly suggests that disrupting the blood vessels in brain tumors might block tumor growth by disrupting brain CSC niches," Gilbertson said. "This is important since the mechanism by which anti-angiogenic drugs, like Avastin, block tumor growth is largely unknown. Our data suggest a previously unrecognized way that anti-angiogenic agents inhibit tumor growth."

The St. Jude investigators have now translated these findings into a clinical trial to determine the effectiveness of Avastin and another drug, Tracevaฎ (erlotinib), in eliminating tumors and preventing their recurrence in children with brain cancers.

The other authors of this study include Christopher Calabrese, Helen Poppleton, Mehmet Kocak, Twala L. Hogg, Christine Fuller, Blair Hamner, Eun Y. Oh, M. Waleed Gaber, David Finklestein, Meredith Allen, Adrian Frank, Ildar T. Bayazitov, Stanislav S. Zakharenko, Amar Gajjar and Andrew Davidoff.

This work was supported in part by the Sontag Foundation, The National Cancer Institute, the V Foundation for Cancer Research and ALSAC.


Story Source:

The above story is based on materials provided by St. Jude Children's Research Hospital. Note: Materials may be edited for content and length.


Cite This Page:

St. Jude Children's Research Hospital. "Vascular Niche Nurtures Brain Tumor Stem Cells." ScienceDaily. ScienceDaily, 19 January 2007. <www.sciencedaily.com/releases/2007/01/070116130945.htm>.
St. Jude Children's Research Hospital. (2007, January 19). Vascular Niche Nurtures Brain Tumor Stem Cells. ScienceDaily. Retrieved April 23, 2014 from www.sciencedaily.com/releases/2007/01/070116130945.htm
St. Jude Children's Research Hospital. "Vascular Niche Nurtures Brain Tumor Stem Cells." ScienceDaily. www.sciencedaily.com/releases/2007/01/070116130945.htm (accessed April 23, 2014).

Share This



More Health & Medicine News

Wednesday, April 23, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Big Pharma Braces for M&A Wave

Big Pharma Braces for M&A Wave

Reuters - Business Video Online (Apr. 22, 2014) — Big pharma on the move as Novartis boss, Joe Jimenez, tells Reuters about plans to transform his company via an asset exchange with GSK, and Astra Zeneca shares surge on speculation that Pfizer is looking for a takeover. Joanna Partridge reports. Video provided by Reuters
Powered by NewsLook.com
How Smaller Plates And Cutlery Could Make You Feel Fuller

How Smaller Plates And Cutlery Could Make You Feel Fuller

Newsy (Apr. 22, 2014) — NBC's "Today" conducted an experiment to see if changing the size of plates and utensils affects the amount individuals eat. Video provided by Newsy
Powered by NewsLook.com
How to Master Motherhood With the Best Work/Life Balance

How to Master Motherhood With the Best Work/Life Balance

TheStreet (Apr. 22, 2014) — In the U.S., there are more than 11 million couples trying to conceive at any given time. From helping celebrity moms like Bethanny Frankel to ordinary soon-to-be-moms, TV personality and parenting expert, Rosie Pope, gives you the inside scoop on mastering motherhood. London-born entrepreneur Pope is the creative force behind Rosie Pope Maternity and MomPrep. She explains why being an entrepreneur offers the best life balance for her and tips for all types of moms. Video provided by TheStreet
Powered by NewsLook.com
Catching More Than Fish: Ugandan Town Crippled by AIDS

Catching More Than Fish: Ugandan Town Crippled by AIDS

AFP (Apr. 22, 2014) — The village of Kasensero on the shores of Lake Victoria was where HIV-AIDS was first discovered in Uganda. Its transient population of fishermen and sex workers means the nationwide programme to combat the virus has had little impact. Duration: 02:30 Video provided by AFP
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