title: High-MET status in non-small cell lung tumors correlates with receptor phosphorylation but not with the serum level of soluble form.
abstract: The receptor tyrosine kinase MET is essential to embryonic development and organ regeneration. Its deregulation is associated with tumorigenesis. While MET gene amplification and mutations leading to MET self-activation concern only a few patients, a high MET level has been found in about half of the non-small cell lung cancers (NSCLCs) tested. How this affects MET activation in tumors is unclear. Also uncertain is the prognostic value, in cancer, of a phenomenon well described in cell models: MET shedding, i.e. its cleavage by membrane proteases leading to release of a soluble fragment into the medium.
  
  
  
  A prospective cohort of 39 NSCLC patients was constituted at diagnosis or soon after. Normal tissues, tumor tissues, and blood samples were obtained. This allowed, for the same patient, synchronous determination of (i) the MET level in the tumor, (ii) receptor phosphorylation, and (iii) the concentration of soluble MET fragment (sMET) in the serum.
  
  
  
  After confirming the adequacy of an ELISA for measuring the serum level of sMET, we found no correlation between this level and the concentration of MET in tumors, as evaluated by immunohistochemistry and western blotting. Nevertheless, all but one tumor displaying a high MET level also displayed receptor phosphorylation, restricted to a small number of tumor cells.
  
  
  
  Our results thus demonstrate that the serum level of sMET is not indicative of the amount of MET present in the tumor cells and cannot be used as a biomarker for therapeutic purposes. However, MET scoring of tumor biopsies could be a first step prior to determination of MET receptor activation in high-MET tumors.
authors: Univ. Lille, CNRS, Institut Pasteur de Lille, UMR 8161 - M3T - Mechanisms of Tumorigenesis and Targeted Therapies, F-59000 Lille, France; Univ. Lille, Institut de Pathologie, CHU Lille, Avenue Oscar Lambret, F-59000 Lille, France.
authors: Marie-Christine
authors: MC
authors: Copin
authors: Univ. Lille, CNRS, Institut Pasteur de Lille, UMR 8161 - M3T - Mechanisms of Tumorigenesis and Targeted Therapies, F-59000 Lille, France.
authors: Marie
authors: M
authors: Lesaffre
authors: Univ. Lille, CNRS, Institut Pasteur de Lille, UMR 8161 - M3T - Mechanisms of Tumorigenesis and Targeted Therapies, F-59000 Lille, France.
authors: Mélanie
authors: M
authors: Berbon
authors: Département de Cancérologie Générale, CLCC Oscar Lambret, 3 rue Fréderic Combemale, Lille 59020, France.
authors: Louis
authors: L
authors: Doublet
authors: Univ. Lille, CNRS, Institut Pasteur de Lille, UMR 8161 - M3T - Mechanisms of Tumorigenesis and Targeted Therapies, F-59000 Lille, France.
authors: Catherine
authors: C
authors: Leroy
authors: Département de Cancérologie Générale, CLCC Oscar Lambret, 3 rue Fréderic Combemale, Lille 59020, France.
authors: Emmanuelle
authors: E
authors: Tresch
authors: Service de Chirurgie Thoracique, Centre Hospitalier Régional Universitaire de Lille, Lille, France.
authors: Henri
authors: H
authors: Porte
authors: Univ. Lille, CNRS, Institut Pasteur de Lille, UMR 8161 - M3T - Mechanisms of Tumorigenesis and Targeted Therapies, F-59000 Lille, France.
authors: Jérôme
authors: J
authors: Vicogne
authors: Univ. Lille, CNRS, Institut Pasteur de Lille, UMR 8161 - M3T - Mechanisms of Tumorigenesis and Targeted Therapies, F-59000 Lille, France; Univ. Lille, CHU Lille, Thoracic Oncology Department, F-59000 Lille, France.
authors: Alexis
authors: A
authors: B Cortot
authors: Département de Cancérologie Générale, CLCC Oscar Lambret, 3 rue Fréderic Combemale, Lille 59020, France.
authors: Eric
authors: E
authors: Dansin
authors: Univ. Lille, CNRS, Institut Pasteur de Lille, UMR 8161 - M3T - Mechanisms of Tumorigenesis and Targeted Therapies, F-59000 Lille, France. Electronic address: david.tulasne@ibl.cnrs.fr.
authors: David
authors: D
authors: Tulasne
mesh_terms: D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000235:genetics* / Q000473:pathology*; D045744:Cell Line, Tumor; D005260:Female; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010766:Phosphorylation; D011446:Prospective Studies; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D059748:Proteolysis; D019859:Proto-Oncogene Proteins c-met / Q000097:blood / Q000235:genetics*
chemical_list: C066855:HGF protein, human; D047428:Protein Kinase Inhibitors; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met
keywords: Hepatocyte growth factor/scatter factor; Lung cancer; MET; Phosphorylation; Proteolytic cleavages; Receptor tyrosine kinase