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 Millions through license revenues
27.04.2017 | Rheinische Friedrich-Wilhelms-Universität Bonn

nachricht New High-Performance Center Translational Medical Engineering
26.04.2017 | Fraunhofer ITEM

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: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Fighting drug resistant tuberculosis – InfectoGnostics meets MYCO-NET² partners in Peru

28.04.2017 | Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

 
Latest News

Wireless power can drive tiny electronic devices in the GI tract

28.04.2017 | Medical Engineering

Ice cave in Transylvania yields window into region's past

28.04.2017 | Earth Sciences

Nose2Brain – Better Therapy for Multiple Sclerosis

28.04.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>