title: Cetuximab treatment alters the content of extracellular vesicles released from tumor cells.
abstract: OBJECTIVE
  Extracellular vesicles (EVs) are attractive candidates for biomarker research, because their content reflects the parental cell status. This study aimed to examine whether tumor cell derived EVs mirrored the cellular changes caused by treatment with cetuximab, a therapeutic antibody that blocks activation of EGF receptor (EGFR).
  
  
  METHODS
  A-431 cells were treated with cetuximab for 48 h. EVs were isolated using differential centrifugation and protein content was analyzed using western blotting.
  
  
  RESULTS
  EV levels of EGFR and phospho-EGFR were reduced after cetuximab treatment, reflecting similar changes in the parental cells. In addition, cetuximab was found associated with EVs.
  
  
  CONCLUSIONS
  EVs could serve as biomarkers to monitor cetuximab treatment. Association of cetuximab with EVs might influence its behavior.
authors.affiliation: Department of Clinical Chemistry & Haematology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands.
authors.forename: Susan M
authors.initials: SM
authors.lastname: van Dommelen
authors.affiliation: Department of Clinical Chemistry & Haematology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands.|Department of Biochemistry & Molecular Biology, The University of British Columbia, Vancouver, BC, V6T 1Z3, Canada.
authors.forename: Roy
authors.initials: R
authors.lastname: van der Meel
authors.affiliation: Department of Clinical Chemistry & Haematology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands.
authors.forename: Wouter W
authors.initials: WW
authors.lastname: van Solinge
authors.affiliation: Department of Pharmaceutics, Utrecht University, Universiteitsweg 99, 3584 CG Utrecht, The Netherlands.
authors.forename: Maria
authors.initials: M
authors.lastname: Coimbra
authors.affiliation: Department of Clinical Chemistry & Haematology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands.
authors.forename: Pieter
authors.initials: P
authors.lastname: Vader
authors.affiliation: Department of Clinical Chemistry & Haematology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands.
authors.forename: Raymond M
authors.initials: RM
authors.lastname: Schiffelers
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D014408:Biomarkers, Tumor / Q000032:analysis / Q000037:antagonists & inhibitors / Q000378:metabolism; D045744:Cell Line, Tumor; D000068818:Cetuximab / Q000494:pharmacology*; D016903:Drug Monitoring; D066246:ErbB Receptors / Q000032:analysis* / Q000037:antagonists & inhibitors / Q000378:metabolism; D000067128:Extracellular Vesicles / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D009369:Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000473:pathology; D010766:Phosphorylation
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; C512478:EGFR protein, human; D066246:ErbB Receptors; D000068818:Cetuximab
keywords: EGFR; biomarker; cancer therapy; cetuximab; diagnostics; exosomes; extracellular vesicles