Primitive cell populations retained from early embryonic development could provide seeds for precancerous growths

July 4, 2012
In the adult stomach (top), ’residual embryonic cells’ (green) are sequestered near the esophagus by mature epithelial cells (pink). Inflammatory damage caused by GERD (middle) disrupts this epithelial layer, and creates opportunities for a REC population to spread — forming a potentially precancerous growth (bottom). © 2011 Elsevier

Heartburn makes for an uncomfortable post-meal experience, but can also herald more serious health concerns. Indeed, gastroesophageal reflux disease (GERD) is a causative factor underlying Barrett’s metaplasia, a condition associated with changes in the epithelial cells lining the esophagus that can ultimately lead to esophageal carcinoma.

Esophageal carcinoma incidence has increased over five-fold in the Western world since 1970, but little is known about its etiology. “The fact that the five-year survival rate has not appreciably changed during this time is demoralizing and suggests that surgery, radiation and chemotherapy have not made a dent in our ability to manage this disease,” says Frank McKeon at the A*STAR Genome Institute of Singapore. However, patients may draw hope from new findings obtained by a team led by McKeon, and Wa Xian of the A*STAR Institute of Medical Biology, using a genetically-modified mouse strain that models Barrett’s metaplasia.

These animals, lacking a protein called p63, exhibited metaplasia in the epithelial where the esophagus meets the stomach. The team, led by McKeon and Xian, observed striking changes in gene expression in this subset of cells, with a strong correlation in the genes that were differentially expressed among p63-deficient mouse tissues and samples from human patients with Barrett’s metaplasia.

The researchers identified two marker proteins that allowed them to visualize the cells that contribute to metaplasia during embryonic development. In wild-type mice, these cells initially line the stomach, but subsequently get displaced by the expansion of a population of p63-expressing . In p63-deficient animals, however, these embryonic epithelial cells linger and turn metaplastic.

Importantly, wild-type mice still retain a population of these cells, dubbed ‘residual embryonic cells’ (RECs), in the stomach region adjacent to the esophagus, and analysis of human tissues revealed a similar population of RECs at the gastroesophageal junction. The researchers hypothesize that these cells represent an ‘opportunistic’ population that is normally prevented from proliferating by fully mature ‘indigenous’ epithelia. By inducing damage to this mature epithelium, may thus allow RECs to proliferate unchecked (see image).

The findings suggest that Barrett’s esophagus does not arise from the typical activating mutations seen in early precursors of cancers, but rather exploits damage to the esophagus in order to expand and grow. This ‘rogue cell’ model could potentially underlie other cancers, and the researchers are now examining whether it is possible to avert esophageal carcinoma by selectively eliminating RECs. “We are identifying unique cell surface targets for targeted therapy to destroy these cells,” say Xian.

Explore further: Leftover embryonic cells connect gastric reflux and cancer

More information: Wang, X. et al. Residual embryonic cells as precursors of a Barrett’s-like metaplasia. Cell 145, 1023–1035 (2012). dx.doi.org/10.1016/j.cell.2011.05.026

Related Stories

Leftover embryonic cells connect gastric reflux and cancer

June 23, 2011
The ultimate source of some cancers is embryonic cells. Research published in the June 24th Cell, a Cell Press publication, traces the precursor of deadly esophageal cancers to leftover embryonic cells found in all adults.

Smoking found to be a risk factor for Barrett's esophagus

April 11, 2012
(HealthDay) -- Cigarette smoking may be a modifiable risk factor for Barrett's esophagus, according to a study published in the April issue of Gastroenterology.

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, ...

Recommended for you

Shooting the achilles heel of nervous system cancers

July 20, 2017
Virtually all cancer treatments used today also damage normal cells, causing the toxic side effects associated with cancer treatment. A cooperative research team led by researchers at Dartmouth's Norris Cotton Cancer Center ...

Molecular changes with age in normal breast tissue are linked to cancer-related changes

July 20, 2017
Several known factors are associated with a higher risk of breast cancer including increasing age, being overweight after menopause, alcohol intake, and family history. However, the underlying biologic mechanisms through ...

Immune-cell numbers predict response to combination immunotherapy in melanoma

July 20, 2017
Whether a melanoma patient will better respond to a single immunotherapy drug or two in combination depends on the abundance of certain white blood cells within their tumors, according to a new study conducted by UC San Francisco ...

Discovery could lead to better results for patients undergoing radiation

July 19, 2017
More than half of cancer patients undergo radiotherapy, in which high doses of radiation are aimed at diseased tissue to kill cancer cells. But due to a phenomenon known as radiation-induced bystander effect (RIBE), in which ...

Definitive genomic study reveals alterations driving most medulloblastoma brain tumors

July 19, 2017
The most comprehensive analysis yet of medulloblastoma has identified genomic changes responsible for more than 75 percent of the brain tumors, including two new suspected cancer genes that were found exclusively in the least ...

Novel CRISPR-Cas9 screening enables discovery of new targets to aid cancer immunotherapy

July 19, 2017
A novel screening method developed by a team at Dana-Farber/Boston Children's Cancer and Blood Disorders Center—using CRISPR-Cas9 genome editing technology to test the function of thousands of tumor genes in mice—has ...

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.