title: Characterization of soluble and exosomal forms of the EGFR released from pancreatic cancer cells.
abstract: OBJECTIVE
  Members of the epidermal growth factor receptor (EGFR) family represent validated targets for anti-cancer therapy and EGFR inhibitors have also shown efficacy in pancreatic carcinoma. We here described in detail molecular forms of the EGF receptor released by pancreatic cancer cells. We found peptides specific for the EGFR in the secretomes of five pancreatic cancer cell lines. Secretomes from cultured cancer cells are widely used as sources for serum biomarker discovery.
  
  
  METHODS
  The detailed analysis of EGFR forms in secretomes of human pancreatic cancer cells is a compilation of results from mass spectrometry (MS) and Western blotting with intracellular and extracellular domain specific antibodies.
  
  
  RESULTS
  Pancreatic cancer cells secrete a 110 kDa soluble form of the EGFR (sEGFR) representing the ligand binding extracellular EGFR domains and presumably released by ectodomain shedding. At the same time, as constituents of exosomes, the EGFR is released as full-length intact receptor (170 kDa) and as a 65 kDa processed form, the C-terminal remnant fragment that corresponds to the intracellular kinase domain.
  
  
  CONCLUSIONS
  The detailed characterization of diverse EGFR forms released by pancreatic cancer cells in vitro and presumably in vivo bears important implications for functional studies, for the validation of soluble EGFR as a serum biomarker and for the design of targeted therapies.
authors.affiliation: Medizinische Universitätsklinik, Knappschaftskrankenhaus, IMBL, Ruhr-Universität Bochum, Bochum, Germany.
authors.forename: Kamila A
authors.initials: KA
authors.lastname: Adamczyk
authors.forename: Susanne
authors.initials: S
authors.lastname: Klein-Scory
authors.forename: Mahnaz Moradian
authors.initials: MM
authors.lastname: Tehrani
authors.forename: Uwe
authors.initials: U
authors.lastname: Warnken
authors.forename: Wolff
authors.initials: W
authors.lastname: Schmiegel
authors.forename: Martina
authors.initials: M
authors.lastname: Schnölzer
authors.forename: Irmgard
authors.initials: I
authors.lastname: Schwarte-Waldhoff
mesh_terms: D015415:Biomarkers / Q000097:blood; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D016895:Culture Media, Serum-Free; D004591:Electrophoresis, Polyacrylamide Gel; D066246:ErbB Receptors / Q000097:blood / Q000737:chemistry / Q000378:metabolism*; D055354:Exosomes / Q000378:metabolism*; D006801:Humans; D010190:Pancreatic Neoplasms / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D012995:Solubility; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D015415:Biomarkers; D016895:Culture Media, Serum-Free; C512478:EGFR protein, human; D066246:ErbB Receptors