Researchers have found that evidence of cachexia, or muscle loss in cancer patients that can be life-threatening, emerges early in tumor development, a discovery that broadens understanding of the complicated effects of cancer on the body and advances their study of the condition to find ways to treat or prevent it.
Cachexia is estimated to cause between 20 and 40 percent of cancer-related deaths, according to the researchers. They studied the development of cachexia in mice, and found that certain conditions associated with muscle wasting occur as early as one week after tumor implantation, weeks before muscle wasting begins. They published their results in the Journal of Cachexia, Sarcopenia and Muscle.
Nic Greene, assistant professor of exercise science in the College of Education and Health Professions at the University of Arkansas, worked with a team of graduate students including Jacob Brown, Megan Rosa-Caldwell and David Lee, as well as Tyrone Washington, associate professor of health, human performance and recreation, and collaborators including Jim Carson from the University of Tennessee Health Center and Michael Wiggs from the University of Texas at Tyler.
In order to learn more about cachexia, the researchers looked at mitochondrial quality in muscle cells.
“Skeletal muscle mass is regulated by a balance between making protein and degrading protein,” Greene. “If you degrade more than you make, you are going to waste. We believe healthy mitochondria are key to prevent the wasting process.”
Mitochondria are often referred to as the “powerhouse of the cell,” because they produce adenosine triphosphate, or ATP, which provides energy for all living cells. These organelles also produce a waste product called reactive oxygen species, or ROS, commonly known as “free radicals.” Impaired mitochondria must work harder to produce ATP, which leads to increased production of free radicals that can degrade the cell health.
The researchers observed both impaired mitochondrial quality and alterations in the cellular functions that are necessary to maintain muscle mass in the mice as early as one week after tumor implantation. These changes were observed several weeks before any signs of muscle wasting appeared. These results are the first step in developing future therapies to address the problem of muscle wasting.
“Cancer cachexia is often not treated before stage IV of cancer is reached,” the researchers write. “These data suggest targeting of muscle mitochondrial quality may be vital for the treatment and prevention of cancer cachexia either pharmacologically or through exercise.”