title: Is there a human homologue to the murine proteolysis-inducing factor?
abstract: OBJECTIVE
  A tumor-derived proteolysis-inducing factor (PIF) is suggested to be a potent catabolic factor in skeletal muscle of mice and humans. We aimed to establish the clinical significance of PIF in cancer patients and to elucidate its structural features.
  
  
  METHODS
  PIF was detected in human urine using a monoclonal antibody (mAb) and related to clinical outcomes. PIF immunoaffinity-purified using the mAb was purified/separated using reverse-phase high-performance liquid chromatography and two-dimensional electrophoresis. Ten human cancer cell lines were tested for expression of mRNA encoding PIF core peptide.
  
  
  RESULTS
  PIF immunoreactivity was present in 160 of 262 patients with advanced cancers of the lung, esophagus/stomach, and other organs. In a Kaplan-Meier survival analysis of 181 lung cancer patients, PIF was unrelated to survival; PIF status was also unrelated to skeletal muscle loss confirmed by computed tomography imaging. PIF was seen in 16 of 24 patients with chronic heart failure and thus is not exclusive to malignant disease. In-gel digestion and mass spectrometric analysis of immunoaffinity purified PIF from cancer patients consistently identified human albumin and immunoglobulins. We showed nonspecific binding of purified albumin and immunoglobulins to the anti-PIF mAb, which is thus not a useful tool for PIF detection or purification in humans. Finally, the human PIF core peptide was detected in human cancer cell lines using reverse transcription-PCR and nucleotide sequencing; however, none of the amplified products had a site for the glycosylation critical to the proteolysis-inducing activity of murine PIF.
  
  
  CONCLUSIONS
  A putative human homologue of murine PIF and its role in human cancer cachexia cannot be verified.
authors.affiliation: Departments of Oncology and Chemistry, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Barbara M
authors.initials: BM
authors.lastname: Wieland
authors.forename: Grant D
authors.initials: GD
authors.lastname: Stewart
authors.forename: Richard J E
authors.initials: RJ
authors.lastname: Skipworth
authors.forename: Kathryn
authors.initials: K
authors.lastname: Sangster
authors.forename: Kenneth C H
authors.initials: KC
authors.lastname: Fearon
authors.forename: James A
authors.initials: JA
authors.lastname: Ross
authors.forename: Tony J
authors.initials: TJ
authors.lastname: Reiman
authors.forename: Jay
authors.initials: J
authors.lastname: Easaw
authors.forename: Marina
authors.initials: M
authors.lastname: Mourtzakis
authors.forename: Vishesh
authors.initials: V
authors.lastname: Kumar
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Pak
authors.forename: Kathryn
authors.initials: K
authors.lastname: Calder
authors.forename: Gerasimos
authors.initials: G
authors.lastname: Filippatos
authors.forename: Dimitris T
authors.initials: DT
authors.lastname: Kremastinos
authors.forename: Monica
authors.initials: M
authors.lastname: Palcic
authors.forename: Vickie E
authors.initials: VE
authors.lastname: Baracos
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001483:Base Sequence; D045744:Cell Line, Tumor; D006031:Glycosylation; D006333:Heart Failure / Q000378:metabolism; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000737:chemistry*; D011509:Proteoglycans / Q000032:analysis* / Q000235:genetics / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D015431:Weight Loss