Characterization of a cancer cachectic factor.
Cancer cachexia is a syndrome of progressive wasting which has been suggested to be mediated by tumour-necrosis factor-alpha, interleukins 1 and 6, interferon-gamma and leukaemia-inhibitory factor. It has proved difficult to correlate levels of tumour-necrosis factor-alpha and interleukin-6 with cancer cachexia, and the weight loss induced by leukaemia-inhibitory factor may be due to toxicity. In the murine adenocarcinoma MAC16, cachexia is mediated by circulatory catabolic factors, which we have now isolated using an antibody cloned from splenocytes of mice transplanted with the MAC16 tumour, with a delayed cachexia. The material is a proteoglycan of relative molecular mass 24K which produces cachexia in vivo by inducing catabolism of skeletal muscle. The 24K material was also present in urine of cachectic cancer patients, but was absent from normal subjects, patients with weight loss due to trauma, and cancer patients with little or no weight loss. This suggests that cachexia in mice and humans may be produced by the same material.
Todorov
P
P
CRC Nutritional Biochemistry Research Group, Pharmaceutical Sciences Institute, Aston University, Birmingham UK.
Cariuk
P
P
McDevitt
T
T
Coles
B
B
Fearon
K
K
Tisdale
M
M
D000230:Adenocarcinoma / Q000737:chemistry / Q000150:complications* / Q000652:urine; D000595:Amino Acid Sequence; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002100:Cachexia / Q000209:etiology* / Q000378:metabolism; D005260:Female; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D009363:Neoplasm Proteins / Q000302:isolation & purification* / Q000494:pharmacology / Q000652:urine; D010190:Pancreatic Neoplasms / Q000737:chemistry / Q000150:complications* / Q000652:urine; D011509:Proteoglycans / Q000302:isolation & purification* / Q000494:pharmacology / Q000652:urine; D014407:Tumor Cells, Cultured
D009363:Neoplasm Proteins; D011509:Proteoglycans