Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Chronic inflammation caused by too little stomach acid leads to gastric cancer

04.04.2005


Genetically engineered mice will help U-M scientists decipher signals that trigger gastric cancer in humans



When it comes to gastric cancer, too little stomach acid can be just as dangerous as too much, according to scientists at the University of Michigan Medical School. Both extremes create inflammatory changes in the stomach lining and a condition called chronic atrophic gastritis, which over time often leads to cancer.

In research published in the March 31 issue of Oncogene, U-M scientists demonstrated that chronic gastritis progresses to gastric cancer in mice with abnormally low levels of gastrin – a hormone that stimulates stomach lining cells called parietal cells to secrete hydrochloric acid. Other researchers have shown that over-production of gastrin in mice stimulates uncontrolled growth of cells in the stomach lining and the development of gastric tumors.


Most physicians are aware of the association between chronic inflammation and gastric cancer. They also know that infection with a bacterium called Helicobacter pylori, if left untreated, can cause stomach cancer. But the fact that lower-than-normal acidity can trigger pre-cancerous changes in the stomach lining is not well-known.

"Our study shows that inflammation, regardless of the cause, is the key to the development of gastric cancer," says Juanita L. Merchant, M.D., Ph.D., a U-M professor of internal medicine and of molecular and integrative physiology. "We’re finding that there are many mechanisms, in addition to gastrin hypersecretion and H. pylori infection, capable of producing the chronic inflammatory changes that lead to cancer."

Most gastric cancers are adenocarcinomas, meaning they develop in epithelial cells lining the stomach. The American Cancer Society estimates that, in 2005, there will be 21,860 new cases of gastric cancer reported in the United States and 11,550 deaths from the disease.

"It’s a fairly deadly type of cancer and difficult to treat, especially in advanced stages," according to Merchant. "Our goal is to identify genetic and molecular changes that occur early – for example, during the inflammatory process before cancer develops – and then see if it is possible to reverse those changes."

Merchant has spent years studying pre-cancerous physical and molecular changes in epithelial cells lining the stomach wall. Now, she has a new research partner – a line of genetically engineered mice that secrete abnormally low amounts of hydrochloric acid, because they lack the gene required to produce gastrin. The mice were generated in the laboratory of Linda C. Samuelson, Ph.D., a professor of molecular and integrative physiology in the U-M Medical School.

The gastrin-deficient mice are especially valuable, because the progression of cell changes leading to gastric cancer in these mice matches changes seen in the development of human gastric cancer. In both species, the process begins with chronic gastritis, which leads to atrophy of the stomach lining, followed by abnormal tissue changes and, finally, the development of malignant cells.

"Now we have a mouse model that we can use to isolate the different genetic steps in human gastric cancer," Merchant says. "We’ve identified certain molecular changes and are in the process of testing these molecules to see how each contributes to the transformation of normal mucosa into gastric cancer."

Three genes of particular interest are RUNX3, TFF1 and STAT3, according to Yana Zavros, Ph.D., a U-M research investigator and first author of the Oncogene paper. "RUNX3 is a stomach-specific tumor suppressor gene whose deletion in mice has been shown to result in gastric cancer," Zavros explains. "TFF1 appears to have a protective effect on the gastric mucosa. STAT3 is a gene that mediates inflammatory signals and has been linked to the development of cancer.

"We are especially interested in RUNX3, because its activity is suppressed in mouse and human gastric cancers," Zavros adds. "Other researchers have shown that RUNX3 stimulates apoptosis or programmed cell death. We hope to learn how the inflammatory process suppresses this critical gene, and subsequently suppresses apoptosis, as well."

Merchant and Zavros believe that suppression of RUNX3’s apoptosis-stimulating signal may be key to the development of gastric cancer, at least in the antrum. They examined gastric tissue from mice in their study using an assay called TUNEL, which detects cells in the process of undergoing apoptosis.

"We found striking differences in the apoptotic rates of parietal cells in the fundus, or upper compartment of the stomach, compared to the antrum where the tumors were developing," Merchant says. "The antrums we studied had a 50-percent to 75-percent decrease in the cell death rate. Rates of cell growth and reproduction were about the same in both stomach compartments.

"So we think that gastric cancer, at least in the antrum, appears to be caused by suppression of the normal rate of apoptosis, rather than by cells growing wildly out of control," Merchant says. "This is a question we will explore in more depth as our research continues."

Sally Pobojewski | EurekAlert!
Further information:
http://www.umich.edu

More articles from Health and Medicine:

nachricht New malaria analysis method reveals disease severity in minutes
14.08.2017 | University of British Columbia

nachricht New type of blood cells work as indicators of autoimmunity
14.08.2017 | Instituto de Medicina Molecular

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

New gene catalog of ocean microbiome reveals surprises

18.08.2017 | Life Sciences

Astrophysicists explain the mysterious behavior of cosmic rays

18.08.2017 | Physics and Astronomy

AI implications: Engineer's model lays groundwork for machine-learning device

18.08.2017 | Information Technology

VideoLinks
B2B-VideoLinks
More VideoLinks >>>