Loss Of Dystrophin: Common Thread In Cancer And MS Muscle Wasting

Recent research conducted at the Ohio State University shows that a wasting condition responsible for nearly a third of cancer deaths involves the loss of an essential muscle protein that is also lost in people with muscular dystrophy.

The study findings, which appear in the November issue of the journal Cancer Cell, show that muscle cells lose significant amounts of the protein dystrophin during cancer wasting, and that subtle changes occur in two other proteins associated with dystrophin in the membrane of muscle cells. These proteins form the dystrophin glycoprotein complex. Dystrophin and DGC are also lost in Duchenne muscular dystrophy.

The loss of dystrophin and damage to the DGC appear to be key players in the development of both cancer wasting and muscular dystrophy.

Cancer wasting occurs most often in esophageal, stomach, colorectal, pancreatic, lung, and head and neck cancers. Cancer patients who develop wasting usually respond more poorly to therapy and have a shorter life span and lower quality of life.

The findings provide a better understanding of cancer wasting, also known as cancer cachexia, a condition first described more than 100 years ago that still lacks effective therapy. The findings also might lead to new ways to diagnose and treat the condition.

Cancer wasting occurs most often in esophageal, stomach, colorectal, pancreatic, lung, and head and neck cancers. The condition is induced by growth of the tumor, and it results in the loss of both fat and skeletal muscle mass. Cancer patients who develop wasting usually respond more poorly to therapy and have a shorter life span and lower quality of life.

Muscular dystrophy is a genetic disease that usually begins in childhood and results in the complete loss of dystrophin and the DGC from muscle.

The researchers found that dystrophin levels were reduced in the muscles of mice with cancer cachexia, and that two DGC proteins were altered. The researchers then showed that cachexia is accelerated in mice that lack dystrophin and develop cancer. Furthermore, they showed that they could prevent cancer wasting in the mice by causing their muscle cells to over-produce dystrophin.

Last, the researchers tested muscle biopsies from 27 patients with gastrointestinal cancers for dystrophin and DGC. Eleven of the patients were confirmed cachectic, and ten of those showed dramatic reductions in dystrophin and significant loss of the DGC.

The authors conclude that the evidence strongly suggests that the wasting conditions in cancer and muscular dystrophy patients are similar, and that the loss of dystrophin and the DGC are important contributing factors in tumor-induced muscle wasting.