Effect of cancer plasma on skeletal muscle metabolism

Circulating factors produced by the macrophages mediate skeletal muscle proteolysis in sepsis and trauma. This study was done to determine whether cytokines affect skeletal muscle metabolism in cancer. Using a method initially developed to measure proteolytic factors in sepsis and trauma, plasma from cachectic cancer patients, noncachectic cancer patients, and normal controls was tested for effects on normal rat skeletal muscle (soleus, extensor digitorum longus). The experimental design allows concomitant measurement of protein synthesis, by [14C]phenylalanine uptake, and protein degradation, by tyrosine release. Plasma from cancer patients caused no acceleration of protein degradation. Noncachectic cancer plasma acted synergistically with insulin to increase protein synthesis (P less than 0.05). These results indicate that a growth factor is present in the plasma of cancer patients who have not become cachexic. To our knowledge, this is the first documentation of a cancer plasma growth factor acting at the organ level to induce synthesis. Our data refute the theory that cancer cachexia is mediated by circulating proteolytic factors. In a separate experiment, purified human recombinant tumor necrosis factor (rTNF) was incubated with normal rat skeletal muscle. No changes were seen in synthesis or degradation rates. Skeletal muscle proteolysis does not appear to be directly induced by rTNF.