Navigation Links
New insights into origin of deadly cancer
Date:6/23/2011

Boston, MAResearchers 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."


'/>"/>

Contact: David Cameron
david_cameron@hms.harvard.edu
617-432-0441
Harvard Medical School
Source:Eurekalert

Related medicine news :

1. Epigenetic study reveals new insights into breast cancer
2. Insights gained from growing cold-causing virus on sinus tissue
3. Bird embryo provides unique insights into development related to cancer and wound healing
4. New insights into cancer treatment
5. Scientists reveal new insights into tendon injury
6. First Look at Prostate Cancer Genome Yields Insights
7. New Insights on Who Should Take Erbitux for Colon Cancer
8. Sodium MRI gives new insights into detecting osteoarthritis, NYU researchers find
9. Snake venom studies yield insights for development of therapies for heart disease and cancer
10. Cell symposia meeting, Influenza: Translating basic insights, to be held Dec. 2-4, 2010
11. From head to toe: Deep insights from whole body MRI
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/25/2016)... , ... June 25, 2016 , ... Austin residents seeking ... American College of Mohs Surgery and to Dr. Russell Peckham for medical and surgical ... effective treatment for skin cancer. The selective fellowship in Mohs Micrographic Surgery completed by ...
(Date:6/25/2016)... (PRWEB) , ... June 25, 2016 , ... ... athletes and non-athletes recover from injury. Recently, he has implemented orthobiologic procedures as ... City area —Johnson is one of the first doctors to perform the treatment. ...
(Date:6/24/2016)... ... 2016 , ... June 19, 2016 is World Sickle Cell Observance Day. In ... benefits of holistic treatments, Serenity Recovery Center of Marne, Michigan, has issued ... Sickle Cell Disease (SCD) is a disorder of the red blood cells, which can ...
(Date:6/24/2016)... ... June 24, 2016 , ... Comfort Keepers® of San Diego, CA is excited ... To Recovery® program to drive cancer patients to and from their cancer treatments. ... highest quality of life and ongoing independence. Getting to and from medical treatments ...
(Date:6/24/2016)... (PRWEB) , ... June 24, 2016 , ... ... client, The Grove Investment Group (TGIG), has initiated cultivation and processing operations at ... Las Vegas and Pahrump, Nevada. , Puradigm is the manufacturer of a complete ...
Breaking Medicine News(10 mins):
(Date:6/23/2016)... June 23, 2016 Research and Markets ... Issue 52" report to their offering. ... treatment creates a favourable commercial environment for MedImmune to enter. ... base that will serve to drive considerable growth for effective ... serve to cap sales considerably, but development is still in ...
(Date:6/23/2016)... , , , WHEN: ... , , , , LOCATION: , , , Online, with ... , EXPERT PANELISTS:  , , , Frost & Sullivan,s Global Vice ... Senior Industry Analyst, Divyaa Ravishankar and Unmesh Lal, Program Manager , ... industry is witnessing an exceptional era. Several new demand spaces, such ...
(Date:6/23/2016)... Colombia , June 23, 2016  Astellas today announced the establishment of Astellas Farma Colombia (AFC), a new ... affiliate in Latin America . ... ... ... ...
Breaking Medicine Technology: