Characterization of a human homologue of proteolysis-inducing factor and its role in cancer cachexia

Constance L. Monitto, Seung Myung Dong, Jin Jen, David Sidransky

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)5862-5869
Number of pages8
JournalClinical Cancer Research
Volume10
Issue number17
DOIs
StatePublished - Sep 1 2004

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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