Nav: Home

Esophageal cancer 'cell of origin' identified

October 11, 2017

NEW YORK, NY (October 11, 2017)--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 esophagus, 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 gastroesophageal reflux disease (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 esophageal adenocarcinoma 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 esophageal cancer 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 cells 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.
-end-
The study is titled, "Transitional basal cells at the squamous-columnar junction generate Barrett's oesophagus." The other contributors are: Haiyan Li (Columbia University Medical Center, New York, NY), Yongchun Zhang (CUMC), Ying Yang (CUMC), Rong Lu (CUMC), Kuancan Liu (CUMC and Fuzhou General Hospital, Fuzhou, Fujian, China), Sijie Lin (CUMC and Fuzhou General Hospital), Xiaopeng Lan (Fuzhou General Hospital), Haikun Wang (Chinese Academy of Sciences, Shanghaim, China), Han Wu (Ascendas Genomics Inc., Zhongshan, Guandong, China), Jian Zhu (University of Rochester, Rochester, NY), Zhongren Zhou (University of Rochester), Jianming Xu (Baylor College of Medicine, Houston, TX), Dong-Kee Lee (Baylor College of Medicine), Lanjing Zhang (University Medical Center of Princeton at Plainsboro, Plainsboro, NJ, and Rutgers University, Newark, NJ), Yuan-Cho Lee (CUMC), Jingsong Yuan (CUMC), Julian A. Abrams (CUMC), Timothy G. Wang (CUMC), Antonia R. Sepulveda (CUMC), Qi Wu (Tianjin Haihe Hospital, Tianjin. China), Huaiyong Chen (Tianjin Haihe Hospital), Xin Sun (Tianjin Haihe Hospital), Junjun She (Xi'an Jiaotong University, Xi'an, China), and Xiaoxin Chen (North Carolina Central University, Durham, NC).

The study was supported by grants from the National Institutes of Health (R01DK113144, R01DK100342, R01HL132996, R01CA112403, and R01CA193455), March of Dimes, Price Family Foundation, the National Key Research and Development Program of China, National Natural Science Foundation of China, the Program for the Top Young Innovative Talents of Fujian Province, and the International Collaborative Project of Fujian Province.

The authors report no financial or other conflicts of interest.

Columbia University Medical Center provides international leadership in basic, preclinical, and clinical research; medical and health sciences education; and patient care. The medical center trains future leaders and includes the dedicated work of many physicians, scientists, public health professionals, dentists, and nurses at the College of Physicians and Surgeons, the Mailman School of Public Health, the College of Dental Medicine, the School of Nursing, the biomedical departments of the Graduate School of Arts and Sciences, and allied research centers and institutions. Columbia University Medical Center is home to the largest medical research enterprise in New York City and State and one of the largest faculty medical practices in the Northeast. The campus that Columbia University Medical Center shares with its hospital partner, NewYork-Presbyterian, is now called the Columbia University Irving Medical Center. For more information, visit cumc.columbia.edu or columbiadoctors.org.

Columbia University Medical Center

Related Stem Cells Articles:

A protein that stem cells require could be a target in killing breast cancer cells
Researchers have identified a protein that must be present in order for mammary stem cells to perform their normal functions.
Approaching a decades-old goal: Making blood stem cells from patients' own cells
Researchers at Boston Children's Hospital have, for the first time, generated blood-forming stem cells in the lab using pluripotent stem cells, which can make virtually every cell type in the body.
New research finds novel method for generating airway cells from stem cells
Researchers have developed a new approach for growing and studying cells they hope one day will lead to curing lung diseases such as cystic fibrosis through 'personalized medicine.'
Mature heart muscle cells created in the laboratory from stem cells
Generating mature and viable heart muscle cells from human or other animal stem cells has proven difficult for biologists.
Mutations in bone cells can drive leukemia in neighboring stem cells
DNA mutations in bone cells that support blood development can drive leukemia formation in nearby blood stem cells.
Scientists take aging cardiac stem cells out of semiretirement to improve stem cell therapy
With age, the chromosomes of our cardiac stem cells compress as they move into a state of safe, semiretirement.
Purest yet liver-like cells generated from induced pluripotent stem cells
A team of researchers from the Medical University of South Carolina and elsewhere has found a better way to purify liver cells made from induced pluripotent stem cells.
Stem cell scientists discover genetic switch to increase supply of stem cells from cord blood
International stem cell scientists, co-led in Canada by Dr. John Dick and in the Netherlands by Dr.
Stem cells from diabetic patients coaxed to become insulin-secreting cells
Signaling a potential new approach to treating diabetes, researchers at Washington University School of Medicine in St.

Related Stem Cells Reading:

Stem Cell Therapy: A Rising Tide: How Stem Cells Are Disrupting Medicine and Transforming Lives
by Neil H Riordan (Author)

Stem Cells: Promise And Reality
by Lygia V Pereira (Author)

Stem Cells: An Insider's Guide
by Paul Knoepfler (Author)

Stem Cells For Dummies
by Lawrence S.B. Goldstein (Author), Meg Schneider (Author)

Stem Cell Revolution: Discover 26 Disruptive Technological Advances to Stem Cell Activation
by Joseph Christiano (Author)

The Stem Cell Revolution
by Mark Berman MD (Author), Elliot Lander MD (Contributor)

Stem Cells: A Very Short Introduction
by Jonathan Slack (Author)

A Buyer's Guide to Stem Cell Therapies: Safely Choose the Right Regenerative Treatment for You

Stem Cells: A Short Course
by Rob Burgess (Author)

Stem Cells Are Everywhere
by Irv Weissman MD (Author)

Best Science Podcasts 2018

We have hand picked the best science podcasts for 2018. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Why We Hate
From bullying to hate crimes, cruelty is all around us. So what makes us hate? And is it learned or innate? This hour, TED speakers explore the causes and consequences of hate — and how we can fight it. Guests include reformed white nationalist Christian Picciolini, CNN commentator Sally Kohn, podcast host Dylan Marron, and writer Anand Giridharadas.
Now Playing: Science for the People

#482 Body Builders
This week we explore how science and technology can help us walk when we've lost our legs, see when we've gone blind, explore unfriendly environments, and maybe even make our bodies better, stronger, and faster than ever before. We speak to Adam Piore, author of the book "The Body Builders: Inside the Science of the Engineered Human", about the increasingly amazing ways bioengineering is being used to reverse engineer, rebuild, and augment human beings. And we speak with Ken Thomas, spacesuit engineer and author of the book "The Journey to Moonwalking: The People That Enabled Footprints on the Moon" about...