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

Human melanoma, G361, which induces cachexia in nude mice, has been shown t o produce a proteolysis-inducing factor (PIF) of M-r 24 000, which is immun ologically identical to that isolated from a cachexia-inducing murine tumou r (MAC16). Biosynthetic labelling of G361 cells using a combination of [S-3 5]sulphate and [6-H-3]glucosamine gave a single component of M-r 24 000 aft er affinity chromatography employing a murine monoclonal antibody. The mate rial contained both radiolabels and, after digestion with peptide N-glycosi dase F, two fragments were produced of M-r 14 000 and 10 000 also containin g both radiolabels. Digestion with O-glycosidase produced three fragments o f M-r 14 000, 6000 and 4000, the first two of which contained both radiolab els; 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 commensu rate 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 polypepti de chain of M-r 4000 with some residual carbohydrate. When PIF from G361 ce lls 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 co mposition analysis showed a significant decrease in the non-fat carcass mas s 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 p roduction of PIF.