title: Endo180 modulation by bisphosphonates and diagnostic accuracy in metastatic breast cancer.
abstract: BACKGROUND
  Endo180 (CD280; MRC2; uPARAP)-dependent collagen remodelling is dysregulated in primary tumours and bone metastasis. Here, we confirm the release and diagnostic accuracy of soluble Endo180 for diagnosing metastasis in breast cancer (BCa).
  
  
  METHODS
  Endo180 was quantified in BCa cell conditioned medium and plasma from BCa patients stratified according to disease status and bisphosphonate treatment (n=88). All P-values are from two-sided tests.
  
  
  RESULTS
  Endo180 is released by ectodomain shedding from the surface of MCF-7 and MDA-MB-231 BCa cell lines. Plasma Endo180 was significantly higher in recurrent/metastatic (1.71±0.87; n=59) vs early/localised (0.92±0.37; n=29) BCa (P<0.0001). True/false-positive rates for metastasis classification were: 85%/50% for the reference standard, CA 15-3 antigen (28 U ml(-1)); ≤97%/≥36% for Endo180; and ≤97%/≥32% for CA 15-3 antigen+Endo180. Bisphosphonate treatment was associated with reduced Endo180 levels in BCa patients with bone metastasis (P=0.011; n=42). True/false-positive rates in bisphosphonate-naive patients (n=57) were: 68%/45% for CA 15-3 antigen; ≤95%/≥20% for Endo180; and ≤92%/≥21% for CA 15-3 antigen+Endo180.
  
  
  CONCLUSIONS
  Endo180 is a potential marker modulated by bisphosphonates in metastatic BCa.
authors.affiliation: Department of Surgery and Cancer, Cancer Research UK Laboratories, Imperial College London, London, UK.
authors.forename: C
authors.initials: C
authors.lastname: Palmieri
authors.forename: M P
authors.initials: MP
authors.lastname: Caley
authors.forename: K
authors.initials: K
authors.lastname: Purshouse
authors.forename: A-V
authors.initials: AV
authors.lastname: Fonseca
authors.forename: M
authors.initials: M
authors.lastname: Rodriguez-Teja
authors.forename: G
authors.initials: G
authors.lastname: Kogianni
authors.forename: L
authors.initials: L
authors.lastname: Woodley
authors.forename: J
authors.initials: J
authors.lastname: Odendaal
authors.forename: K
authors.initials: K
authors.lastname: Elliott
authors.forename: J
authors.initials: J
authors.lastname: Waxman
authors.forename: J
authors.initials: J
authors.lastname: Sturge
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood*; D001859:Bone Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000556:secondary; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000473:pathology; D004164:Diphosphonates / Q000627:therapeutic use; D005260:Female; D006801:Humans; D011975:Receptors, Mitogen / Q000097:blood*
chemical_list: D014408:Biomarkers, Tumor; D004164:Diphosphonates; C408294:Endo180; D011975:Receptors, Mitogen