Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Neurotransmitters signal aggressive cancer, offer potential for early diagnosis


Nerves talk to each other using chemicals called neurotransmitters. One of those "communication chemicals," aptly named GABA (gamma amino butyric acid), shows up in unusually high amounts in some aggressive tumors, according to a new study from Washington University School of Medicine in St. Louis.

The researchers investigated metastatic neuroendocrine tumors, which include aggressive types of lung, thyroid, and prostate cancers that spread to other parts of the body. Their study will appear in the July 12 issue of the Proceedings of the National Academy of Sciences and is available online after July 4.

"GABA appears to be an indicator of a bad prognosis for these cancers," says Jeffrey I. Gordon, M.D., director of the Center for Genome Sciences at Washington University. "But there’s hope in our ability to identify substances, like GABA, that are associated with metastatic tumors. Usually these tumors are diagnosed only after they have spread to other parts of the body, but now we have the potential to recognize them before they metastasize."

Elevated amounts of GABA were discovered in an analysis of aggressive neuroendocrine prostate tumors in genetically engineered mice. Along with GABA, two other substances were seen, one a related neurotransmitter and the other a plant growth hormone with an unknown function in animals. Furthermore, the researchers found that the tumors made GABA using a different set of biochemical reactions than normal. Key enzymes involved in the production of these compounds were switched on in poor prognosis malignant metastatic tumors.

"The mouse model was an important beginning point for our investigation," says the study’s lead author Joseph E. Ippolito, a graduate research assistant in the University’s NIH-supported Medical Scientist Training Program. "We took information about what genes were expressed in the mouse tumors, made computer-assisted predictions about what type of metabolism was going on in these abnormal cells compared to their normal non-cancerous counterparts, and used new, powerful metabolite detectors to verify that these compounds were actually being made. We then took information gained from the mouse and asked whether the same human genes are expressed in poor prognosis as opposed to good prognosis human tumors. We found that the human genes that give rise to the key enzymes required to produce these metabolites were invariably switched on the poor prognosis but not the good prognosis tumor groups."

"Most people understand the revolution in medicine to be a DNA-centered search for mutations in genes that cause disease. This study illustrates another layer of the revolution - understanding how certain diseases, in this case cancer, are linked to abnormalities in cellular metabolism - an area called ’metabolomics’. We’ve described a unique tumor-associated pattern that we hope will provide new ways to diagnose these poor prognosis cancers earlier and to implement more effective treatments" Gordon says.

The researchers believe that metastatic neuroendocrine tumor cells use GABA signaling processes to communicate with each other and with their environment. "Through carefully planned clinical trials, we may be able to evaluate the therapeutic potential of already available drugs that affect GABA signaling to treat these aggressive types of cancers," says Ippolito.

The association of GABA with aggressive tumors was uncovered by a novel combination of techniques that can now be employed for further identification of substances linked to tumors and other diseases. The resulting information will significantly advance diagnosis and treatment options.

"We used a way to cross from basic sequence information in genomes to information about the substances likely to arise in tumors" says Ippolito.

The research team first analyzed the activity of genes in the mouse tumors using GeneChips, miniaturized arrays of gene sequences, to obtain information about how active each gene in tumors is.

They combined the mouse data with parallel data from 182 human tumors. Then, the gene-activity data was fed into sophisticated software that supplied the researchers with a prediction about which metabolic reactions were revved up in the tumors and which were slowed down. The last piece of the puzzle was supplied by a highly sensitive instrument, called a mass spectrometer, that measured the products of cellular metabolism. The mass spectrometer measurements were cross-checked with the gene activity data and the predictions of metabolic reactions. This set of techniques demonstrated the linkage of abnormal GABA production to aggressive tumors.

"We are able to examine not just genes, not just proteins, but the chemistry that underlies diseased tissues," Gordon says. "Computational, experimental and instrumental tools are now available to tackle metabolomics and then translate lessons learned at the laboratory bench to the patient’s bedside as called for by the University’s BioMed 21 initiative."

BioMed 21 is a strategic research initiative that aims to rapidly translate genomic science into patient care. It includes faculty from the schools of Medicine, Engineering & Applied Science and Arts & Sciences.

Gwen Ericson | EurekAlert!
Further information:

More articles from Life Sciences:

nachricht Microbe hunters discover long-sought-after iron-munching microbe
24.10.2016 | Max-Planck-Institut für marine Mikrobiologie

nachricht Seeking balanced networks: how neurons adjust their proteins during homeostatic scaling.
24.10.2016 | Max-Planck-Institut für Hirnforschung

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

Im Focus: Diamonds aren't forever: Sandia, Harvard team create first quantum computer bridge

By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.

"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...

Im Focus: New Products - Highlights of COMPAMED 2016

COMPAMED has become the leading international marketplace for suppliers of medical manufacturing. The trade fair, which takes place every November and is co-located to MEDICA in Dusseldorf, has been steadily growing over the past years and shows that medical technology remains a rapidly growing market.

In 2016, the joint pavilion by the IVAM Microtechnology Network, the Product Market “High-tech for Medical Devices”, will be located in Hall 8a again and will...

Im Focus: Ultra-thin ferroelectric material for next-generation electronics

'Ferroelectric' materials can switch between different states of electrical polarization in response to an external electric field. This flexibility means they show promise for many applications, for example in electronic devices and computer memory. Current ferroelectric materials are highly valued for their thermal and chemical stability and rapid electro-mechanical responses, but creating a material that is scalable down to the tiny sizes needed for technologies like silicon-based semiconductors (Si-based CMOS) has proven challenging.

Now, Hiroshi Funakubo and co-workers at the Tokyo Institute of Technology, in collaboration with researchers across Japan, have conducted experiments to...

All Focus news of the innovation-report >>>



Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

Seeking balanced networks: how neurons adjust their proteins during homeostatic scaling.

24.10.2016 | Life Sciences

Resolving the mystery of preeclampsia

21.10.2016 | Health and Medicine

Stanford researchers create new special-purpose computer that may someday save us billions

21.10.2016 | Information Technology

More VideoLinks >>>