Role of a proteolysis inducing factor (PIF) in cachexia induced by a human melanoma (G361)

Human melanoma, G361, which induces cachexia in nude mice, has been shown to produce a proteolysis-inducing factor (PIF) of M-r 24 000, which is immunologically identical to that isolated from a cachexia-inducing murine tumour (MAC16). Biosynthetic labelling of G361 cells using a combination of [S-35]sulphate and [6-H-3]glucosamine gave a single component of M-r 24 000 after affinity chromatography employing a murine monoclonal antibody. The material contained both radiolabels and, after digestion with peptide N-glycosidase F, two fragments were produced of M-r 14 000 and 10 000 also containing both radiolabels. Digestion with O-glycosidase produced three fragments of M-r 14 000, 6000 and 4000, the first two of which contained both radiolabels; while the third only contained H-3. This digestion pattern is the same as that previously observed with PIF from the MAC16 tumour and is commensurate with one N-linked sulphated oligosaccharide chain of M-r 10 000, one O-linked sulphated oligosaccharide chain of M-r 6000 and a central polypeptide chain of M-r 4000 with some residual carbohydrate. When PIF from G361 cells was administered to female NMRI mice (20 g) a pronounced depression of body weight (1.36 +/- 0.36 g; P < 0.0001 from control) was observed over a 24 h period without a decrease in either food or water consumption. Body composition analysis showed a significant decrease in the non-fat carcass mass without a change in carcass fat or body water. This result suggests that depletion of lean body mass in mice bearing G361 melanoma arises from the production of PIF.