Changes in myostatin signaling in non-weight-losing cancer patients.

Abstract

Myostatin is a negative regulator of skeletal muscle mass. We recently demonstrated that myostatin expression is upregulated in an experimental model of cancer cachexia, suggesting that modulations of this pathway might play a pathogenic role in cancer-related muscle wasting. The present study was designed to investigate whether myostatin signaling is modulated in the muscle of non-weight-losing (nWL) patients with lung and gastric cancer. Myostatin signaling was studied in muscle biopsies obtained during surgical procedure from nWL patients affected by gastric (n=16) or lung (n=17) cancer. Western blotting was applied to test both the total expression of myostatin and the expression of phosphorylated form of GSK-3beta and Smad2/3. In patients with gastric cancer, the expression of both myostatin and phosphorylated GSK-3beta (p-GSK3β) were significantly increased. By contrast, in patients with lung cancer, myostatin levels were comparable to controls, whereas the expression of p-GSK3β significantly decreased in patients with disease stage III/IV. Myostatin signaling is altered in nWL cancer patients. Different tumor types may give rise to different patterns of molecular changes within the muscle, which occur even before cachexia becomes clinically apparent.