Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New insights into origin of deadly cancer

24.06.2011
Barrett’s esophagus, often a precursor to esophageal cancer, results from residual, embryonic cells

Researchers have discovered a new mechanism for the origin of Barrett's esophagus, an intestine-like growth in the esophagus that is triggered by chronic acid reflux and often progresses to esophageal cancer. Studying mice, the researchers found that Barrett's esophagus arises not from mutant cells in the esophagus but rather a small group of previously overlooked cells present in all adults that can rapidly expand to cancer precursors when the normal esophagus is damaged by acid.

This research will be published online in the June 24th issue of Cell.

Decades of cancer research tells us that most of the common cancers begin with genetic changes that occur over a period of 15 to 20 years, in some cases leading to aggressive cancers. However, for a subset of cancers that appear to be linked to chronic inflammation, this model might not hold.

Barrett's esophagus, which was first described by the Australian surgeon Norman Barrett in 1950, affects two to four million Americans. In this condition, tissue forms in the esophagus that resembles the intestinal tissue normally located much farther down the digestive tract. As a result, a person's chances of developing a deadly esophageal adenocarcinoma increase by 50- to 150-fold. Late stage treatment is largely palliative, so it is important to understand how acid reflux triggers it in the first place.

Research from the laboratory of Frank McKeon, Harvard Medical School professor of cell biology, together with Wa Xian, a postdoctoral researcher at Brigham and Women's Hospital and the Institute of Medical Biology, Singapore, along with an international consortium including Christopher Crum, director of Women's and Perinatal Pathology at Brigham and Women's Hospital, has shown that Barrett's esophagus originates from a minor population of non-esophageal cells left over from early development.

For the past decade, McKeon and his laboratory have been using mouse models to investigate the role of p63, a gene involved in the self-renewal of epithelial stem cells including those of the esophagus. McKeon joined forces two years ago with Wa Xian, an expert in signal transduction in cancer cells, to tackle the vexing problem of the origin of Barrett's esophagus.

At that time, the dominant hypothesis for Barrett's was that acid reflux triggers the esophageal stem cells to make intestine cells rather than normal esophageal tissue. However, McKeon and Xian felt the support for this concept was weak. Taking a different track, they studied a mouse mutant lacking the p63 gene and mimicked the symptoms of acid reflux. As a result, the entire esophagus was covered with a Barrett's-like tissue that proved to be a near exact match with human Barrett's at the gene expression level.

The researchers were particularly surprised by the sheer speed with which this Barrett's esophagus appeared in the mice.

"From the speed alone we knew we were dealing with something different here," said Xia Wang, postdoctoral fellow at Harvard Medical School and co-first author of this work.

Yusuke Yamamoto, a postdoctoral fellow at the Genome Institute of Singapore and also co-first author, added that, "we just had to track the origins of the Barrett's cells back through embryogenesis using our markers from extensive bioinformatics."

In essence, the investigators tracked the precancerous growth to a discrete group of leftover embryonic cells wedged between the junction of the esophagus and the stomach--precisely where endoscopists have argued Barrett's esophagus begins. As predicted by the mouse studies, the researchers identified a group of embryonic cells exactly at the junction between the esophagus and the stomach in all normal humans.

"Barrett's arises from this discrete group of pre-existing, residual embryonic cells present in all adults that seemingly lie-in-wait for a chance to take over when the esophagus is damaged," said McKeon. Added Xian, "We know these embryonic cells have different gene expression patterns from all normal tissues and this makes them inviting targets for therapies to destroy Barrett's before it progresses to cancer."

The therapeutic opportunities of this work are potentially immense.

"We are directing monoclonal antibodies to cell surface markers that can identify these precursor cells, so we may have a new opportunity to intervene therapeutically and prevent Barrett's esophagus in at-risk patients," said Wa Xian.

"Additionally," noted McKeon, "we are cloning the stem cells for both these precursors and for Barrett's esophagus itself, and these should represent critical targets for both monoclonal antibodies and small molecule inhibitors."

Finally, there is reason to believe that this unusual mechanism might apply to a subset of other lethal cancers with unsure origins.

Crum noted that "some very aggressive cancers arise at junctions of two tissues and these deserve closer scrutiny to get at their origins if we are to surmount these diseases."

This work was supported by the National Institutes of Health.

David Cameron | EurekAlert!
Further information:
http://www.hms.harvard.edu

More articles from Health and Medicine:

nachricht 3D images of cancer cells in the body: Medical physicists from Halle present new method
16.05.2018 | Martin-Luther-Universität Halle-Wittenberg

nachricht Better equipped in the fight against lung cancer
16.05.2018 | Friedrich-Alexander-Universität Erlangen-Nürnberg

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: Explanation for puzzling quantum oscillations has been found

So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics

Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...

Im Focus: Dozens of binaries from Milky Way's globular clusters could be detectable by LISA

Next-generation gravitational wave detector in space will complement LIGO on Earth

The historic first detection of gravitational waves from colliding black holes far outside our galaxy opened a new window to understanding the universe. A...

Im Focus: Entangled atoms shine in unison

A team led by Austrian experimental physicist Rainer Blatt has succeeded in characterizing the quantum entanglement of two spatially separated atoms by observing their light emission. This fundamental demonstration could lead to the development of highly sensitive optical gradiometers for the precise measurement of the gravitational field or the earth's magnetic field.

The age of quantum technology has long been heralded. Decades of research into the quantum world have led to the development of methods that make it possible...

Im Focus: Computer-Designed Customized Regenerative Heart Valves

Cardiovascular tissue engineering aims to treat heart disease with prostheses that grow and regenerate. Now, researchers from the University of Zurich, the Technical University Eindhoven and the Charité Berlin have successfully implanted regenerative heart valves, designed with the aid of computer simulations, into sheep for the first time.

Producing living tissue or organs based on human cells is one of the main research fields in regenerative medicine. Tissue engineering, which involves growing...

Im Focus: Light-induced superconductivity under high pressure

A team of scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg investigated optically-induced superconductivity in the alkali-doped fulleride K3C60under high external pressures. This study allowed, on one hand, to uniquely assess the nature of the transient state as a superconducting phase. In addition, it unveiled the possibility to induce superconductivity in K3C60 at temperatures far above the -170 degrees Celsius hypothesized previously, and rather all the way to room temperature. The paper by Cantaluppi et al has been published in Nature Physics.

Unlike ordinary metals, superconductors have the unique capability of transporting electrical currents without any loss. Nowadays, their technological...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Save the date: Forum European Neuroscience – 07-11 July 2018 in Berlin, Germany

02.05.2018 | Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

Unique scope of UV LED technologies and applications presented in Berlin: ICULTA-2018

12.04.2018 | Event News

 
Latest News

Supersonic waves may help electronics beat the heat

18.05.2018 | Power and Electrical Engineering

Keeping a Close Eye on Ice Loss

18.05.2018 | Information Technology

CrowdWater: An App for Flood Research

18.05.2018 | Information Technology

VideoLinks
Science & Research
Overview of more VideoLinks >>>