Purification and characterization of a tumor lipid-mobilizing factor.
Cancer patients with weight loss showed urinary excretion of a lipid-mobilizing factor (LMF), determined by the ability to stimulate lipolysis in isolated murine epididymal adipocytes. Such bioactivity was not detectable in the urine of cancer patients without weight loss or in normal subjects. The LMF was purified using a combination of ion exchange, exclusion, and hydrophobic interaction chromatographies to give a single component of apparent Mr 43,000, which showed homology in amino acid sequence with human plasma Zn-alpha2-glycoprotein. Both substances showed the same mobility on denaturing and nondenaturing gels and the same chymotrypsin digestion pattern, both stained heavily for carbohydrate, and they showed similar immunoreactivity. Polyclonal antisera to human plasma Zn-alpha2-glycoprotein was also capable of neutralization of the bioactivity of human LMF in vitro. Using competitive PCR to quantify expression of Zn-alpha2-glycoprotein, we found that only those tumors that were capable of producing a decrease in carcass lipid expressed mRNA for Zn-alpha2-glycoprotein. These results provide strong evidence to suggest that tumor production of Zn-alpha2-glycoprotein is responsible for the lipid catabolism seen in cancer patients.
Todorov
P T
PT
Pharmaceutical Sciences Institute, Aston University, Birmingham, United Kingdom.
McDevitt
T M
TM
Meyer
D J
DJ
Ueyama
H
H
Ohkubo
I
I
Tisdale
M J
MJ
D017667:Adipocytes / Q000187:drug effects; D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D001798:Blood Proteins / Q000737:chemistry / Q000378:metabolism; D002100:Cachexia / Q000150:complications / Q000652:urine*; D002478:Cells, Cultured; D002852:Chromatography, Ion Exchange; D004067:Digestive System Neoplasms / Q000150:complications / Q000652:urine*; D004822:Epididymis; D005260:Female; D006023:Glycoproteins / Q000235:genetics / Q000652:urine*; D006801:Humans; D008053:Lipid Mobilization; D008066:Lipolysis / Q000187:drug effects; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008970:Molecular Weight; D009374:Neoplasms, Experimental / Q000652:urine; D010051:Ovarian Neoplasms / Q000150:complications / Q000652:urine*; D010455:Peptides / Q000302:isolation & purification / Q000494:pharmacology / Q000652:urine*; D016133:Polymerase Chain Reaction; D011509:Proteoglycans; D029589:Seminal Plasma Proteins; D000090203:Zn-Alpha-2-Glycoprotein
D000911:Antibodies, Monoclonal; D001798:Blood Proteins; D006023:Glycoproteins; D010455:Peptides; D011509:Proteoglycans; D029589:Seminal Plasma Proteins; D000090203:Zn-Alpha-2-Glycoprotein; C008287:lipid mobilizing substance; C042057:proteolysis-inducing peptide