Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Cancer Wasting Due in Part to Tumor Factors That Block Muscle Repair, Study Shows

24.10.2013
- Cancer wasting causes 20-25 percent of cancer deaths.
- Tumor growth causes the condition, which has no treatment.
- This study shows that cancer wasting is due in part to tumor factors that block muscle repair, and it suggests a new avenue for treating the disease.

A new study reveals that tumors release factors into the bloodstream that inhibit the repair of damaged muscle fibers, and that this contributes to muscle loss during cancer wasting.

The condition, also called cancer cachexia, accompanies certain types of cancer, causes life-threatening loss of body weight and lean muscle mass, and is responsible for up to one-in-four cancer deaths. There is no treatment for the condition.

The study was led by researchers at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James), and it points to new strategies and new drug targets for treating cancer cachexia.

The findings were published in the Journal of Clinical Investigation.

The researchers looked at muscle stem cells, which are also called satellite cells. These cells are associated with muscle fibers and are essential for repairing damaged fibers. Normally, damage to muscle fibers causes these stem cells to proliferate and to differentiate into mature muscle cells. These muscle cells then fuse with damaged surrounding fibers to limit muscle wasting. This process is blocked during cancer cachexia, the researchers say.

“Our study showed that although muscle stem cells are activated during cachexia, factors released by the tumor block these cells from differentiating into muscle cells, which leaves them unable to repair cachectic muscle fibers,” says principal investigator Denis Guttridge, PhD, professor of molecular virology, immunology and medical genetics and a member of the OSUCCC – James Molecular Biology and Cancer Genetics Program.

“By identifying agents that overcome the block and allow muscle stem cells to differentiate, it might be possible to restore muscle mass and enhance the quality of life of cancer patients with cachexia,” he says.

For this study, Guttridge and his colleagues used animal models and tissue from cachectic pancreatic-cancer patients to identify factors in the muscle microenvironment that contribute to cancer cachexia. Key findings include:

Cachexia is associated with tumor-induced damage to skeletal muscle cells and tumor-induced proliferation of muscle stem cells;

Overexpression of the muscle stem cell factor, Pax7, blocks the cells’ ability to differentiate and promotes cancer-induced wasting;

The overexpression of Pax7 promotes cancer wasting by blocking the maturation of muscle cells and their fusion with surrounding fibers, which allows muscle to gain mass;

The overexpression of Pax7 is controlled by NF-kappa B (NF-kB), which has been shown to play multiple roles in cancer. In cachexia, NF-kB causes the deregulation of Pax7 expression, which in turn impairs differentiation of muscle progenitor cells and promotes muscle atrophy;

Because of its tissue specificity, Pax7 inhibition might offer an attractive therapy for cancer cachexia.

“For decades, studies in cachexia have focused on mechanisms that lead to muscle wasting from within skeletal muscle fibers,” Guttridge says. “Our study is the first to show proof of concept that events occurring outside the muscle fiber and within the muscle microenvironment also play a part in driving muscle wasting in cancer.”

Funding from the National Institutes of Health(NIH)/National Cancer Institute (grants CA097953, CA098466, CA124692) and the NIH/Center for Clinical and Translational Science (grant UL1TR000090) supported this research.

Other researchers involved in this study were first author Wei He, Jingxin Wang, Mark Bloomston, Peter Muscarella, Peter Nau, Nilay Shah, Matthew E.R. Butchbach and Katherine Ladner, The Ohio State University; Emanuele Berardi, Veronica M. Cardillo, Paola Aulino, Sergio Adamo, Dario Coletti, Sapienza University, Rome, Italy; Swarnali Acharyya, Memorial Sloan Kettering Cancer Center; Jennifer Thomas-Ahner, Federica Montanaro, Nationwide Children’s Hospital; Michael A. Rudnicki, Ottawa Health Research Institute, Ottawa, Ontario, Canada; Charles Keller, Oregon Health and Science University.

The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute strives to create a cancer-free world by integrating scientific research with excellence in education and patient-centered care, a strategy that leads to better methods of prevention, detection and treatment. Ohio State is one of only 41 National Cancer Institute (NCI)-designated Comprehensive Cancer Centers and one of only four centers funded by the NCI to conduct both phase I and phase II clinical trials. The NCI recently rated Ohio State’s cancer program as “exceptional,” the highest rating given by NCI survey teams. As the cancer program’s 228-bed adult patient-care component, The James is a “Top Hospital” as named by the Leapfrog Group and one of the top cancer hospitals in the nation as ranked by U.S.News & World Report.

Contact: Darrell E. Ward, Wexner Medical Center Public Affairs and Media Relations,

614-293-3737, or Darrell.Ward@osumc.edu

Darrell E. Ward | EurekAlert!
Further information:
http://www.osumc.edu

More articles from Studies and Analyses:

nachricht Study relating to materials testing Detecting damages in non-magnetic steel through magnetism
23.07.2018 | Technische Universität Kaiserslautern

nachricht Innovative genetic tests for children with developmental disorders and epilepsy
11.07.2018 | Christian-Albrechts-Universität zu Kiel

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

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

Im Focus: It’s All in the Mix: Jülich Researchers are Developing Fast-Charging Solid-State Batteries

There are currently great hopes for solid-state batteries. They contain no liquid parts that could leak or catch fire. For this reason, they do not require cooling and are considered to be much safer, more reliable, and longer lasting than traditional lithium-ion batteries. Jülich scientists have now introduced a new concept that allows currents up to ten times greater during charging and discharging than previously described in the literature. The improvement was achieved by a “clever” choice of materials with a focus on consistently good compatibility. All components were made from phosphate compounds, which are well matched both chemically and mechanically.

The low current is considered one of the biggest hurdles in the development of solid-state batteries. It is the reason why the batteries take a relatively long...

Im Focus: Color effects from transparent 3D-printed nanostructures

New design tool automatically creates nanostructure 3D-print templates for user-given colors
Scientists present work at prestigious SIGGRAPH conference

Most of the objects we see are colored by pigments, but using pigments has disadvantages: such colors can fade, industrial pigments are often toxic, and...

Im Focus: Unraveling the nature of 'whistlers' from space in the lab

A new study sheds light on how ultralow frequency radio waves and plasmas interact

Scientists at the University of California, Los Angeles present new research on a curious cosmic phenomenon known as "whistlers" -- very low frequency packets...

Im Focus: New interactive machine learning tool makes car designs more aerodynamic

Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.

When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...

Im Focus: Robots as 'pump attendants': TU Graz develops robot-controlled rapid charging system for e-vehicles

Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.

Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

LaserForum 2018 deals with 3D production of components

17.08.2018 | Event News

Within reach of the Universe

08.08.2018 | Event News

A journey through the history of microscopy – new exhibition opens at the MDC

27.07.2018 | Event News

 
Latest News

Air pollution leads to cardiovascular diseases

21.08.2018 | Ecology, The Environment and Conservation

Researchers target protein that protects bacteria's DNA 'recipes'

21.08.2018 | Life Sciences

A paper battery powered by bacteria

21.08.2018 | Power and Electrical Engineering

VideoLinks
Science & Research
Overview of more VideoLinks >>>