Navigation Links
Metabolic molecule drives growth of aggressive brain cancer

COLUMBUS, Ohio A study led by researchers at The Ohio State University Comprehensive Cancer Center Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC James) has identified an abnormal metabolic pathway that drives cancer-cell growth in a particular glioblastoma subtype. The finding might lead to new therapies for a subset of patients with glioblastoma, the most common and lethal form of brain cancer.

The physician scientists sought to identify glioblastoma subtype-specific cancer stem cells. Genetic analyses have shown that high-grade gliomas can be divided into four subtypes: proneural, neural, classic and mesenchymal.

This study shows that the mesenchymal subtype is the most aggressive subtype, that it has the poorest prognosis among affected patients, and that cancer stem cells isolated from the mesenchymal subtype have significantly higher levels of the enzyme ALDH1A3 compared with the proneural subtype.

The findings, published recently in the Proceedings of the National Academy of Sciences, show that high levels of the enzyme drive tumor growth.

"Our study suggests that ALDH1A3 is a potentially functional biomarker for mesenchymal glioma stem cells, and that inhibiting that enzyme might offer a promising therapeutic approach for high-grade gliomas that have a mesenchymal signature," says principal investigator Ichiro Nakano, MD, PhD, associate professor of neurosurgery at the OSUCCC James. "This indicates that therapies for high-grade gliomas should be personalized, that is, based on the tumor subtype instead of applying one treatment to all patients," he says.

The National Cancer Institute estimates that 23,130 Americans will be diagnosed with brain and other nervous system tumors in 2013, and that 14,000 people will die of these malignancies. Glioblastoma accounts for about 15 percent of all brain tumors, is resistant to current therapies and has a survival as short as 15 months after diagnosis.

Little is known, however, about the metabolic pathways that drive the growth of individual glioblastoma subtypes knowledge that is crucial for developing novel and effective targeted therapies that might improve treatment for these lethal tumors.

For this study, Nakano and his collaborators used cancer cells from 40 patients with high-grade gliomas, focusing on tumor cells with a stem-cell signature. The researchers then used microarray analysis and pre-clinical animal assays to identify two predominant glioblastoma subtypes, proneural and mesenchymal.

Key technical findings include:

  • Genes involved in glycolysis and gluconeogenesis, particularly ALDH1A3, were significantly up-regulated in mesenchymal glioma stem cells compared to proneural stem cells;
  • Mesenchymal glioma stem cells show significantly higher radiation resistance and high expression of DNA-repair genes;
  • Radiation induces transformation of proneural glioma stem cells into mesenchymal-like glioma stem cells that are highly resistant to radiation treatment; inhibiting the ALDH1 pathway reverses this resistance.
  • Inhibiting ALDH1A3-mediated pathways slows the growth of mesenchymal glioma stem cells and might provide a promising therapeutic approach for glioblastomas with a mesenchymal signature.

"Overall, our data suggest that a novel signaling mechanism underlies the transformation of proneural glioma stem cells to mesenchymal-like cells and their maintenance as stem-like cells," Nakano says. Currently, their discoveries are in provision patent application, led by the Technology Licensing Office at University of Pittsburgh.


Contact: Darrell E. Ward
Ohio State University Medical Center

Related medicine news :

1. Metabolic PET imaging provides earlier warning of coronary disease
2. hCGTreatments / Diet Doc hCG Diets & Weight Loss Plans Offer Improved hCG Diets to Counteract Metabolic Slowdown
3. Roundworm quells obesity and related metabolic disorders
4. Metabolic disorders predict the hardening of the arterial walls already in childhood
5. Epoxide hydrolase inhibition and Thiazolidinediones: A therapy for cardiometabolic syndrome
6. Monounsaturated fats reduce metabolic syndrome risk
7. Monosaturated fats reduce metabolic syndrome risk
8. Altman Fitness Launches the Metabolic Typing - Customized Nutrition Plan
9. EU funds research project on obesity and metabolic complications
10. Selexis SA Announces Publication in Metabolic Engineering of Data Demonstrating Improvement of Therapeutic Protein Secretion with Engineered CHO Cells
11. Recon 2 modeling may help tailor treatments for patients with metabolic diseases, cancer
Post Your Comments:
(Date:10/13/2017)... CT (PRWEB) , ... October 13, 2017 , ... ... long-term care services, staged a mock evacuation of the facility as part of a ... Shelton Fire Department, Echo Hose EMS and Shelton City Emergency Manager, as well as ...
(Date:10/13/2017)... ... 13, 2017 , ... Ellevate Network, the leading network for professional women, brought ... gender equality at their inaugural Summit in New York City in June. The event ... audience of over 3 million. To watch the Mobilize Women video, click here ...
(Date:10/13/2017)... ... ... Talented host, actor Rob Lowe, is introducing a segment ... of "Success Files," which is an award-winning educational program broadcasted on PBS Member ... with passion and integrity. , Sciatica occurs when the sciatic nerve in the ...
(Date:10/13/2017)... ... 2017 , ... “America On The Brink”: the Christian history of the United ... the creation of published author, William Nowers. Captain Nowers and his wife, Millie, ... spent thirty years in the Navy. Following his career as a naval aviator ...
(Date:10/12/2017)... ... October 12, 2017 , ... Planet Fitness, one of the largest and ... plans to open a flagship location in Covington, LA at 401 N. U.S. Highway ... store next to Office Depot in the Holiday Square shopping center. Its location allows ...
Breaking Medicine News(10 mins):
(Date:10/11/2017)... Oct. 11, 2017  True Health, a leader ... its effort during National Breast Cancer Awareness month ... risks. Research ... calculated that more than 10 million American women ... in BRCA1 or BRCA2 and have not had testing. ...
(Date:10/7/2017)...   Provista, a proven leader in the ... purchasing power, today announced a new resource area on ... is the online home for case studies, articles ... news releases, slideshows and events. ... resources at their fingertips, viewers can also watch short ...
(Date:10/4/2017)... Mass. , Oct. 4, 2017 ... of single-use, self-contained, illuminating medical devices, today announced ... National Health Surveillance Agency (or Agência Nacional de ... The first single-use, cordless surgical retractor with integrated ... provides optimal access, illumination and exposure of a ...
Breaking Medicine Technology: