Navigation Links
Leftover embryonic cells connect gastric reflux and cancer

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.

Some people with gastric reflux disease have a greater risk of developing esophageal cancer. These patients often have Barrett's esophagus, a condition in which intestinal-like cells appear in the esophagus. Esophageal cancers are difficult to treat and, together with gastric adenocarcinomas, kill more than a million people each year.

"A lot of cancers you can do little about, and new drugs are approved based on their ability to extend life by one or two months," said the senior author of this study, Frank McKeon of Harvard Medical School and the Genome Institute of Singapore. "Focus on the precursors of cancer may be our best hope for medicine. Here, we are looking at a precursor of a cancer precursor that is present in all of us."

"It's not clear that the embryonic stem cell precursors have any real purpose," says study author Wa Xian. "Methods to rid the body of those cells may therefore be the easiest and most cost-effective way to stop the disease before it even starts, particularly for those at the greatest risk."

The prevailing theory has been that the abnormal cells seen in Barrett's esophagus arise as the normal squamous stem cells "transcommit" in response to acid-reflux to a new, intestine-like fate. Using a mouse model of chronic acid-reflux disease, , Xian and McKeon now show that, even as embryos, the animals showed a vast expanse of intestine-like cells in their esophaguses with gene expression profiles very similar to those seen in Barrett's.

"The metaplasia developed very quickly, in a matter of days," Xian said. "This was shocking to us as we generally consider cancer precursors taking multiple genetic 'hits' and years to develop."

The speedy development suggested that the precancerous condition wasn't related to the slow accumulation of mutations. Their findings also argue against the idea that the normal stem cells were undergoing a change of fate.

The mice under study lack a gene called p63 that is required for the self-renewal of stem cells in all stratified epithelial tissues. Because of their genetic defect, the mice are born without the squamous epithelium that normally lines the esophagus. "Without p63, the stem cells run out of gas and cease to exist," McKeon said. "You can't transcommit a cell that isn't there."

The gene profiles of those cells were also very different from cells of the intestine, despite their intestine-like appearance. "It's not a transcommitment," Xian said. "The Barrett's structure has its own cellular origin."

The researchers also generated mouse models in which the esophageal tissue could be damaged at precise times, revealing that this damage triggers a rapid mobilization of embryonic cells that would otherwise be resting. Those cells take up the newly freed space in a process that might mimic the evolution of Barrett's. Again, the speed with which those cells were activated seemed to rule out mutations as an explanation in favor of competition between normal cells and the minority embryonic population.

"The dim prognosis for esophageal adenocarcinoma has driven therapeutic strategies aimed at destroying Barrett's esophagus, including Radio Frequency Ablation (RFA), before it progresses to aggressive cancer," McKeon said. "While RFA appears to be exceedingly effective in the short term, there are hints that Barrett's might be fairly resilient and poised for recurrence."

The new findings suggest it may be more effective to go after the precursor cells instead. To do that, Xian says they "will have to clone the stem cell for Barrett's and the Barrett's precursor cell in the junction to find the targets needed to eradicate them."

In a final note, McKeon and Xian say that they suspect an additional subset of cancers, especially those linked to inflammation and tissue damage, might arise from precursors derived in a manner similar to Barrett's. "If so, we anticipate rapid progress into a group of particularly aggressive cancers that typically outwit the best treatments we have."


Contact: Elisabeth (Lisa) Lyons
Cell Press

Related medicine news :

1. Oxycontin Abusers Often Rely on Leftover Meds From Friends
2. Stem cells from surgery leftovers could repair damaged hearts
3. Gene Holds Key to Embryonic Stem Cell Rejuvenation
4. NIA researchers find gene to explain mouse embryonic stem cell immortality
5. New Period of Brain ‘Plasticity' Created with Transplanted Embryonic Cells
6. Embryonic stem cells reveal oncogenes secret growth formula
7. Without this protein, embryonic development halts
8. Therapeutic potential of embryonic stem cells
9. Chromosomal variations found in early passage female embryonic stem cells
10. UCLA scientists isolate the first stages of tissue production in human embryonic stem cells
11. Human embryonic stem cells purified in new, rapid technique
Post Your Comments:
(Date:11/30/2015)... ... November 30, 2015 , ... ... teams looking to maximize recovery through quality sleep. Tim DiFrancesco, training coach for ... a better night’s sleep. ChiliPad precisely regulates the surface temperature of each side ...
(Date:11/30/2015)... NJ (PRWEB) , ... November 30, 2015 , ... Dr. ... With three office locations, patients can visit Dr. Margulies to experience the best available ... to hold the title of "NJ Top Dentist"! , Orthodontics is the branch of ...
(Date:11/30/2015)... ... November 30, 2015 , ... The recently published ... Data System (NPDS) reveals that in 2014, someone called a poison center about ... million of which were human exposure cases. , The American Association of Poison ...
(Date:11/30/2015)... ... November 30, 2015 , ... The American Society for Clinical Pathology (ASCP) announced ... Day 2015. On Nov. 30, ASCP shared its “Give a minute. Get tested. Find ... and the importance of getting tested for HIV. , ASCP has asked members to ...
(Date:11/30/2015)... PITTSBURGH, PA (PRWEB) , ... November 30, 2015 , ... ... scoop often results in wasted time. Fortunately, an inventor from Chesterfield, Va., has found ... SCOOP CLIP to keep the scoop used to measure powdered contents in a canister ...
Breaking Medicine News(10 mins):
(Date:11/30/2015)... Nov. 30, 2015   Royal Philips (NYSE: ... the industry,s first MRI guided user interface and automatic ... patients with MR Conditional implants, such as knee and ... 2015 Radiological Society of North America Annual Meeting (RSNA) ... supports diagnostic confidence of this growing patient population. ScanWise ...
(Date:11/30/2015)... RATON, Fla. , Nov. 30, 2015   ... (the Institute) announced today that it has finalized ... device start-up company with technology developed at Florida State ... publicly-funded research, and bridges early funding gaps for companies ... and research institutions. --> ...
(Date:11/30/2015)... , Nov. 30, 2015 Baxalta ... biopharmaceutical leader dedicated to delivering transformative therapies ... medical conditions, today announced the launch and ... PEGylated], an extended circulating half-life recombinant factor ... on full-length ADVATE [Antihemophilic Factor (Recombinant)]. The ...
Breaking Medicine Technology: