title: Glycoprotein nonmetastatic B is an independent prognostic indicator of recurrence and a novel therapeutic target in breast cancer.
abstract: OBJECTIVE
  Although the murine orthologue of glycoprotein nonmetastatic B (GPNMB), Osteoactivin, promotes breast cancer metastasis in an in vivo mouse model, its importance in human breast cancer is unknown. We have examined the significance of GPNMB expression as a prognostic indicator of recurrence and assessed its potential as a novel therapeutic target in breast cancer.
  
  
  METHODS
  The clinical significance of GPNMB expression in breast cancer was addressed by analyzing GPNMB levels in several published gene expression data sets and two independent tissue microarrays derived from human breast tumors. GPNMB-expressing human breast cancer cell lines were further used to validate a toxin-conjugated anti-GPNMB antibody as a novel therapeutic agent.
  
  
  RESULTS
  GPNMB expression correlates with shorter recurrence times and reduced overall survival of breast cancer patients. Epithelial-specific GPNMB staining is an independent prognostic indicator for breast cancer recurrence. GPNMB is highly expressed in basal and triple-negative breast cancers and is associated with increased risk of recurrence within this subtype. GPNMB expression confers a more migratory and invasive phenotype on breast cancer cells and sensitizes them to killing by CDX-011 (glembatumumab vedotin), a GPNMB-targeted antibody-drug conjugate.
  
  
  CONCLUSIONS
  GPNMB expression is associated with the basal/triple-negative subtype and is a prognostic marker of poor outcome in patients with breast cancer. CDX-011 (glembatumumab vedotin) is a promising new targeted therapy for patients with metastatic triple-negative breast cancers, a patient population that currently lacks targeted-therapy options.
authors.affiliation: Department of Medicine, Goodman Cancer Research Centre, McGill University, 1160 Pine Avenue West Montréal, Québec, Canada, H3A 1A3.
authors.forename: April A N
authors.initials: AA
authors.lastname: Rose
authors.forename: Andrée-Anne
authors.initials: AA
authors.lastname: Grosset
authors.forename: Zhifeng
authors.initials: Z
authors.lastname: Dong
authors.forename: Caterina
authors.initials: C
authors.lastname: Russo
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Macdonald
authors.forename: Nicholas R
authors.initials: NR
authors.lastname: Bertos
authors.forename: Yves
authors.initials: Y
authors.lastname: St-Pierre
authors.forename: Ronit
authors.initials: R
authors.lastname: Simantov
authors.forename: Michael
authors.initials: M
authors.lastname: Hallett
authors.forename: Morag
authors.initials: M
authors.lastname: Park
authors.forename: Louis
authors.initials: L
authors.lastname: Gaboury
authors.forename: Peter M
authors.initials: PM
authors.lastname: Siegel
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000906:Antibodies / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000008:administration & dosage; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D002277:Carcinoma / Q000175:diagnosis* / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D018796:Immunoconjugates; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D009842:Oligopeptides / Q000627:therapeutic use; D011379:Prognosis; D012008:Recurrence; D016019:Survival Analysis; D023041:Xenograft Model Antitumor Assays
chemical_list: D000906:Antibodies; D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; C503042:GPNMB protein, human; D018796:Immunoconjugates; D008562:Membrane Glycoproteins; D009842:Oligopeptides; C551271:glembatumumab vedotin