Guttridge and a group of colleagues began this study after noticing that mice with cancer cachexia showed damage to the membranes of their muscle cells, as in muscular dystrophy. This caused them to suspect that dystrophin and the DGC might be involved.

In muscle cells, the long, thin dystrophin molecule joins the cell skeleton to the DGC located in the membrane. The DGC is a cluster of proteins that extends from the membrane into the surrounding tissue and anchors the muscle cell in place. Dystrophin works like a shock absorber during muscle contraction.

"Dystrophin prevents the cell membrane from being torn by the shear forces produced during muscle contraction," says first author Swarnali Acharyya, a pre-doctoral student in Guttridge's laboratory.

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.

Overall, Guttridge says, "our evidence strongly suggests that the loss of dystrophin and the DGC are important contributing factors in tumor-induced muscle wasting."

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Contact: Darrell E. Ward
Darrell.Ward@osumc.edu
614-293-3737
Ohio State University
14-Nov-2005