Metabolic and morphological alterations induced by proteolysis-inducing factor from Walker tumour-bearing rats in C2C12 myotubes

BACKGROUND: Patients with advanced cancer suffer from cachexia, which is characterised by a marked weight loss, and is invariably associated with the presence of tumoral and humoral factors which are mainly responsible for the depletion of fat stores and muscular tissue. METHODS: In this work, we used cytotoxicity and enzymatic assays and morphological analysis to examine the effects of a proteolysis-inducing factor (PIF)-like molecule purified from ascitic fluid of Walker tumour-bearing rats (WF), which has been suggested to be responsible for muscle atrophy, on cultured C2C12 muscle cells. RESULTS: WF decreased the viability of C2C12 myotubes, especially at concentrations of 20-25 mug.mL-1. There was an increase in the content of the pro-oxidant malondialdehyde, and a decrease in antioxidant enzyme activity. Myotubes protein synthesis decreased and protein degradation increased together with an enhanced in the chymotrypsin-like enzyme activity, a measure of functional proteasome activity, after treatment with WF. Morphological alterations such as cell retraction and the presence of numerous cells in suspension were observed, particularly at high WF concentrations. CONCLUSION: These results indicate that WF has similar effects to those of proteolysis-inducing factor, but is less potent than the latter. Further studies are required to determine the precise role of WF in this experimental model. © 2008 Yano et al; licensee BioMed Central Ltd.

Are tumoral factors responsible for host tissue wasting in cancer cachexia?

Both cytokines and tumor factors have been implicated in tissue loss in cancercachexia. Loss of adipose tissue is most likely due to the tumor (and host) factorzinc-α2-glycoprotein because of its direct lipolytic effect, ability to sensitizeadipocytes to lipolytic stimuli and increased expression in cachexia. TNF-α andthe tumor factor proteolysis-inducing factor are the major contenders for skeletalmuscle at rophy; both increase protein degradat ion through theubiquitin-proteasome pathway and depres s protein synthesis throughphosphorylation of eukaryotic initiation factor 2α. However, while most studiesreport proteolysis-inducing factor levels to correlate with the appearance ofcachexia, there is some disagreement regarding a correlation between serumlevels of TNF-α and weight loss. Furthermore, only antagonists to proteolysisinducingfactor prevent muscle loss in cancer patients, suggesting that tumorfactors are the most important. © 2010 Future Medicine Ltd.