Characterization of a human homologue of proteolysis-inducing factor and its role in cancer cachexia.
Cachexia is an important cause of secondary morbidity and mortality in patients with cancer. Previous studies have suggested that cancer-associated cachexia may be due in part to tumor-specific production and secretion of a glycosylated peptide, proteolysis-inducing factor, originally identified in a murine cancer cachexia model. We report here the cloning of a human cDNA that generates a peptide having high-sequence homology to this proteolysis-inducing factor. Constitutive expression of human proteolysis-inducing factor is low or absent in most normal human tissues but appears to be elevated in some human tumors. Stable forced expression of human proteolysis-inducing factor in multiple murine and human cell lines results in a secreted protein, but no glycosylation of the protein is detected. In addition, tumor xenografts engineered to overexpress human proteolysis-inducing factor protein do not induce cachexia in vivo. These findings raise important questions as to potential cross-species differences in protein sequence and processing of murine proteolysis-inducing factor and human proteolysis-inducing factor, as well as the nature of the relationship between human proteolysis-inducing factor and the development of cancer cachexia.
Monitto
Constance L
CL
Department of Anesthesiology and Critical Care Medicine, Johns Hopkins Hospital, Baltimore, Maryland, USA.
Dong
Seung-Myung
SM
Jen
Jin
J
Sidransky
David
D
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001798:Blood Proteins / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002100:Cachexia / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000032:analysis; D005260:Female; D006031:Glycosylation; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008969:Molecular Sequence Data; D010957:Plasmids; D011509:Proteoglycans; D012333:RNA, Messenger / Q000378:metabolism; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured / Q000637:transplantation
D001798:Blood Proteins; D018076:DNA, Complementary; D011509:Proteoglycans; D012333:RNA, Messenger; C042057:proteolysis-inducing peptide