Navigation Links
Glutamine ratio is key ovarian cancer indicator
Date:5/5/2014

HOUSTON -- (May 5, 2014) -- A Rice University-led analysis of the metabolic profiles of hundreds of ovarian tumors has revealed a new test to determine whether ovarian cancer cells have the potential to metastasize, or spread to other parts of the body. The study also suggests how ovarian cancer treatments can be tailored based on the metabolic profile of a particular tumor.

The research, which appears online this week in Molecular Systems Biology, was conducted at the Texas Medical Center in Houston by researchers from Rice, the University of Texas MD Anderson Cancer Center and Baylor College of Medicine.

"We found a striking difference between the metabolic profiles of poorly aggressive and highly aggressive ovarian tumor cells, particularly with respect to their production and use of the amino acid glutamine," said lead researcher Deepak Nagrath of Rice. "For example, we found that highly aggressive ovarian cancer cells are glutamine-dependent, and in our laboratory studies, we showed that depriving such cells of external sources of glutamine -- as some experimental drugs do -- was an effective way to kill late-stage cells.

"The story for poorly aggressive cells was quite different," said Nagrath, assistant professor of chemical and biomolecular engineering and of bioengineering at Rice. "These cells use an internal metabolic pathway to produce a significant portion of the glutamine that they consume, so a different type of treatment -- one aimed toward internal glutamine sources -- will be needed to target cells of this type."

The research is part of a growing effort among cancer researchers worldwide to create treatments that target the altered metabolism of cancer cells. It has long been known that cancer cells adjust their metabolism in subtle ways that allow them to proliferate faster and survive better. In 1924, Otto Warburg showed that cancer cells produced far more energy from glycolysis than did normal cells. The Nobel Prize-winning discovery became known as the "Warburg effect," and researchers long believed that all cancers behaved in this way. Intense research in recent decades has revealed a more nuanced picture.

"Each type of cancer appears to have its own metabolic signature," Nagrath said. "For instance, kidney cancer does not rely on glutamine, and though breast cancer gets some of its energy from glutamine, it gets even more from glycolysis. For other cancers, including glioblastoma and pancreatic cancer, glutamine appears to be the primary energy source."

Nagrath, director of Rice's Laboratory for Systems Biology of Human Diseases, said the new metabolic analysis indicates that ovarian cancer may be susceptible to multidrug cocktails, particularly if the amounts of the drugs can be tailored to match the metabolic profile of a patient's tumor.

The research also revealed a specific biochemical test that pathologists could use to guide such treatments. The test involves measuring the ratio between the amount of glutamine that a cell takes up from outside and the amount of glutamine it makes internally.

"This ratio proved to be a robust marker for prognosis," said MD Anderson co-author Anil Sood, professor of gynecologic oncology and reproductive medicine and co-director of the Center for RNA Interference and Non-Coding RNA. "A high ratio was directly correlated to tumor aggression and metastatic capability. Patients with this profile had the worst prognosis for survival."

The three-year study included cell culture studies at Rice as well as a detailed analysis of gene-expression profiles of more than 500 patients from the Cancer Genome Atlas and protein-expression profiles from about 200 MD Anderson patients.

"The enzyme glutaminase is key to glutamine uptake from outside the cell, and glutaminase is the primary target that everybody is thinking about right now in developing drugs," Nagrath said. "We found that targeting only glutaminase will miss the less aggressive ovarian cancer cells because they are at a metabolic stage where they are not yet glutamine-dependent."

Rice graduate student Lifeng Yang, lead author of the study, designed a preclinical experiment to test the feasibility of a multidrug approach. He used a drug to inhibit the early stage production of internal glutamine while also limiting the uptake of external glutamine.

"That depleted all sources of glutamine for the cells, and we found that cell proliferation decreased significantly," Yang said.

Nagrath said the study also revealed another key finding -- a direct relationship between glutamine and an ovarian cancer biomarker called STAT3.

"A systems-level understanding of the interactions between metabolism and signaling is vital to developing novel strategies to tackle cancer," said MD Anderson co-author Prahlad Ram, associate professor of systems biology and co-director of the MD Anderson Cancer Center's Systems Biology Program. "STAT3 is the primary marker that is used today to ascertain malignancy, tumor aggression and metastasis in ovarian cancer."

Nagrath said, "The higher STAT3 is, the more aggressive the cancer. For the first time, we were able to show how glutamine regulates STAT3 expression through a well-known metabolic pathway called the TCA cycle, which is also known as the Krebs cycle."

Nagrath said the research is ongoing. Ultimately, he hopes the investigations will lead to new treatment regimens for cancer as well as a better understanding of the role of cancer-cell metabolism in metastasis and drug resistance.


'/>"/>

Contact: Jade Boyd
jadeboyd@rice.edu
713-348-6778
Rice University
Source:Eurekalert  

Related biology news :

1. Increasing sugar concentration in tomato juice
2. UNC researchers link aging to cellular interactions that occur across generations
3. Researchers question published no-till soil organic carbon sequestration rates
4. Sibling cooperation in earwig families gives clues to early evolution of social behavior
5. Gene linked to pediatric kidney cancer suggests new strategies for kidney regeneration
6. Gothenburg scientist in Nature: Climate models underestimate costs to future generations
7. Next-generation glaucoma therapeutics hold considerable promise
8. Global research possibilities expand as IISD assumes operation of Canadas famed Experimental Lakes
9. Energy Systems Integration Facility named Lab of the Year
10. Research center to develop next generation of advanced chemical products
11. Optimal duration of percutaneous microballoon compression for trigeminal nerve injury
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Glutamine ratio is key ovarian cancer indicator
(Date:1/11/2017)... Jan. 11, 2017 Intoxalock, a leading ignition ... release of its patent-pending calibration device. With this new ... calibrations, securely upload data logs and process repairs at ... "Fighting drunk driving through the application of ... at large, but also for the customer who can ...
(Date:1/6/2017)... -- Delta ID Inc., a leader in consumer-grade iris scanning ... CES® 2017. Delta ID has collaborated with Gentex Corporation ... of iris scanning as a secure, reliable and convenient ... car, and as a way to elevate the security ... ID and Gentex will demonstrate (booth #7326 LVCC) a ...
(Date:12/22/2016)... -- As part of its longstanding mission to improve genetic literacy ... released its latest children,s book, titled The One ... topics of inheritance and variation of traits that are part ... school classrooms in the US. The book ... Killoran , whose previous book with 23andMe, You ...
Breaking Biology News(10 mins):
(Date:1/13/2017)... , Jan 13, 2017 Research and Markets has ... to their offering. ... global biopolymers market to grow at a CAGR of 16.83% during the ... the growth prospects of the global biopolymers market for 2017-2021. To calculate ... of sales of biopolymer products. The report also includes a a discussion ...
(Date:1/12/2017)... ... January 12, 2017 , ... ... VTI, Vertebral Technologies, Inc., announces the successful outcome of the first lumbar ... 2016, VTI (Vertebral Technologies, Inc.) has partnered with Mexico-based medical product company ...
(Date:1/12/2017)... ... January 12, 2017 , ... ... treatments, 26-year-old Lisa Rosendahl’s doctors gave her only a few months to live. ... drug combination that has stabilized Rosendahl’s disease and increased both the quantity and ...
(Date:1/12/2017)... PUNE, India , January 12, 2017 The report "Direct-Fed ... Aquatic Animals), Form (Dry and Liquid), and Region - Global Forecast to 2022", ... 934.5 Million in 2016 and projected to reach USD 1,399.6 Million by 2022, ... Reading ... MarketsandMarkets Logo ...
Breaking Biology Technology: