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 Smart Data Transformation – Surfing the Big Wave
02.12.2016 | Fraunhofer-Institut für Angewandte Informationstechnik FIT

nachricht Climate change could outpace EPA Lake Champlain protections
18.11.2016 | University of Vermont

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: Electron highway inside crystal

Physicists of the University of Würzburg have made an astonishing discovery in a specific type of topological insulators. The effect is due to the structure of the materials used. The researchers have now published their work in the journal Science.

Topological insulators are currently the hot topic in physics according to the newspaper Neue Zürcher Zeitung. Only a few weeks ago, their importance was...

Im Focus: Significantly more productivity in USP lasers

In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.

Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...

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...

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

Researchers identify potentially druggable mutant p53 proteins that promote cancer growth

09.12.2016 | Life Sciences

Scientists produce a new roadmap for guiding development & conservation in the Amazon

09.12.2016 | Ecology, The Environment and Conservation

Satellites, airport visibility readings shed light on troops' exposure to air pollution

09.12.2016 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>