Are Tumoral Factors Responsible for Host Tissue Wasting in Cancer Cachexia?

Both cytokines and tumor factors have been implicated in tissue loss in cancer cachexia. Loss of adipose tissue is most likely due to the tumor (and host) factor zinc-alpha2-glycoprotein because of its direct lipolytic effect, ability to sensitize adipocytes to lipolytic stimuli and increased expression in cachexia. TNF-alpha and the tumor factor proteolysis-inducing factor are the major contenders for skeletal muscle atrophy; both increase protein degradation through the ubiquitin-proteasome pathway and depress protein synthesis through phosphorylation of eukaryotic initiation factor 2 alpha. However, while most studies report proteolysis-inducing factor levels to correlate with the appearance of cachexia, there is some disagreement regarding a correlation between serum levels of TNF-alpha and weight loss. Furthermore, only antagonists to proteolysis inducing factor prevent muscle loss in cancer patients, suggesting that tumor factors are the most important.