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 Study suggests possible new target for treating and preventing Alzheimer's
02.12.2016 | Oregon Health & Science University

nachricht The first analysis of Ewing's sarcoma methyloma opens doors to new treatments
01.12.2016 | IDIBELL-Bellvitge Biomedical Research Institute

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: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

Im Focus: Molecules change shape when wet

Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water

In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

IHP presents the fastest silicon-based transistor in the world

05.12.2016 | Power and Electrical Engineering

InLight study: insights into chemical processes using light

05.12.2016 | Materials Sciences

High-precision magnetic field sensing

05.12.2016 | Power and Electrical Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>