Esophageal cancer 'cell of origin' identified

October 11, 2017
Arrows point to a population of unique basal progenitor cells (p63+ KRT7+ Claudin18-) located at the equivalent of the gastroesophageal junction in a mouse model. Credit: Lab of Jianwen Que, MD, PhD, Columbia University Medical Center

Columbia University Medical Center (CUMC) researchers have identified cells in the upper digestive tract that can give rise to Barrett's esophagus, a precursor to esophageal cancer. The discovery of this "cell of origin" promises to accelerate the development of more precise screening tools and therapies for Barrett's esophagus and esophageal adenocarcinoma, the fastest growing form of cancer in the U.S.

The findings, made in mice and in human tissue, were published in today's online edition of Nature.

In Barrett's , some of the tissue in the tube connecting the mouth to the stomach are replaced by intestinal-like tissue, causing heartburn and difficulty swallowing. Most cases of Barrett's stem from (GERD)—chronic regurgitation of acid from the stomach into the lower esophagus. A small percentage of people with Barrett's esophagus develop esophageal adenocarcinoma, the most common form of esophageal cancer.

Incidence of has risen by 800 percent over the past four decades. However, there has been little progress in screening and treatment over the same period. If is not detected early, patients typically survive less than a year after diagnosis.

Researchers have proposed at least five models of Barrett's esophagus, each based on a different cell type. "However, none of these experimental models mimics all of the characteristics of the condition," said study leader Jianwen Que, MD, PhD, associate professor of medicine at CUMC. "This led us to believe that there must be another, yet-to-be-discovered, cell of origin for Barrett's esophagus."

In the current study, Dr. Que and his colleague Ming Jiang, PhD, an associate research scientist in CUMC's Department of Medicine and first author of the paper, genetically altered mice to promote the development of Barrett's esophagus. His team then examined the mice's gastroesophageal junction tissue for changes. "All of the known in this tissue remained the same, but we found a previously unidentified zone populated by unique basal progenitor cells," he said. Progenitor cells are early descendants of stem cells that can differentiate into one or more specific cell types.

Dr. Que's team then performed a technique called lineage tracing to determine if these unique basal progenitor cells, tagged with a fluorescent protein, can give rise to Barrett's esophagus. In the tests, several mouse models were used to show that bile acid reflux or genetic changes promote expansion of these cells, leading to the development of Barrett's esophagus. The same observations were made in organoids (artificially grown masses of cells that resemble an organ) created from unique basal progenitor cells that were isolated from the gastroesophageal junction in mice and humans.

"Now that we know the cell of origin for Barrett's esophagus, the next step is to develop therapies that target these cells or the signaling pathways that are activated by acid reflux," said Dr. Que.

The study is titled, "Transitional basal cells at the squamous-columnar junction generate Barrett's oesophagus."

Explore further: Research in fruit flies provides new insight into Barrett's esophagus

More information: Ming Jiang et al, Transitional basal cells at the squamous–columnar junction generate Barrett's oesophagus, Nature (2017). DOI: 10.1038/nature24269

Related Stories

Research in fruit flies provides new insight into Barrett's esophagus

June 27, 2013
Research focused on the regulation of the adult stem cells that line the gastrointestinal tract of Drosophila suggests new models for the study of Barrett's esophagus. Barrett's esophagus, a risk factor for esophageal cancer, ...

New studies add to understanding of treatments for Barrett's esophagus

October 6, 2017
The October issue of GIE: Gastrointestinal Endoscopy features several new studies evaluating various treatments for Barrett's esophagus (BE). Two of these studies are highlighted below.

Team discovers stem cells in the esophagus

October 16, 2014
Despite previous indications to the contrary, the esophagus does have its own pool of stem cells, said researchers from the University of Pittsburgh School of Medicine in an animal study published online today in Cell Reports. ...

Risk of esophageal cancer in patients with Barrett’s esophagus

October 14, 2011
(Medical Xpress) -- A new study published in the New England Journal of Medicine reveals that the risk of patients with Barrett’s esophagus developing adenocarcinoma of the esophagus are not as high as once originally ...

Study reveals origins of esophageal cancer

January 17, 2012
(Medical Xpress) -- Researchers at Columbia University Medical Center (CUMC) have identified the critical early cellular and molecular events that give rise to a type of esophageal cancer called esophageal adenocarcinoma, ...

Barrett's with irregular Z line unlikely to progress quickly

April 12, 2017
(HealthDay)—There is a low risk of development of high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC) among patients with Barrett's esophagus (BE) of

Recommended for you

Big Data shows how cancer interacts with its surroundings

October 23, 2017
By combining data from sources that at first seemed to be incompatible, UC San Francisco researchers have identified a molecular signature in tissue adjacent to tumors in eight of the most common cancers that suggests they ...

Symptom burden may increase hospital length of stay, readmission risk in advanced cancer

October 23, 2017
Hospitalized patients with advanced cancer who report more intense and numerous physical and psychological symptoms appear to be at risk for longer hospital stays and unplanned hospital readmissions. The report from a Massachusetts ...

CAR-T immunotherapy may help blood cancer patients who don't respond to standard treatments

October 20, 2017
Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine in St. Louis is one of the first centers nationwide to offer a new immunotherapy that targets certain blood cancers. Newly approved ...

Researchers pinpoint causes for spike in breast cancer genetic testing

October 20, 2017
A sharp rise in the number of women seeking BRCA genetic testing to evaluate their risk of developing breast cancer was driven by multiple factors, including celebrity endorsement, according to researchers at the University ...

Study shows how nerves drive prostate cancer

October 19, 2017
In a study in today's issue of Science, researchers at Albert Einstein College of Medicine, part of Montefiore Medicine, report that certain nerves sustain prostate cancer growth by triggering a switch that causes tumor vessels ...

Gene circuit switches on inside cancer cells, triggers immune attack

October 19, 2017
Researchers at MIT have developed a synthetic gene circuit that triggers the body's immune system to attack cancers when it detects signs of the disease.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.