title: Mechanisms of local invasion in enteroendocrine tumors: identification of novel candidate cytoskeleton-associated proteins in an experimental mouse model by a proteomic approach and validation in human tumors.
abstract: Small-intestinal neuroendocrine tumors (SI-NETs) are defined as locally invasive only after extension to the muscularis propria. To gain further insight into the molecular mechanisms, we applied a proteomic approach to an orthotopic xenograft model to identify candidate proteins evaluable in human SI-NETs. After grafting STC-1 neuroendocrine tumor cells on the caecum of nude mice, comparative proteomic studies were performed between the pre-invasive and the invasive stages, respectively 2 and 8 weeks after grafting. We identified 24 proteins displaying at least a 1.5-fold differential expression between 2 and 8 week-stages. Most were cytoskeleton-associated proteins, among which five showed decreasing expression levels (CRMP2, TCP1ε, TPM2, vimentin, desmin) and two increasing expression levels (14-3-3γ, CK8). Changes for CRMP2, TCP1ε, TPM2 and 14-3-3γ were confirmed in experimental tumors and in a series of 28 human SI-NETs. In conclusion, our results underline the relevance of proteomics to identify novel biomarkers of tissue invasion.
authors.affiliation: INSERM, U1052, CNRS, UMR5286, Centre de Recherche en Cancérologie de Lyon, Equipe «Différenciation Endocrine et Tumorigenèse», Faculté Laënnec, Université Lyon 1, Lyon F-69372, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Couderc
authors.affiliation: INSERM, U1052, CNRS, UMR5286, Centre de Recherche en Cancérologie de Lyon, Equipe «Différenciation Endocrine et Tumorigenèse», Faculté Laënnec, Université Lyon 1, Lyon F-69372, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Bollard
authors.affiliation: INSERM, U1038, CEA iRTSV, Biologie à Grande Echelle, Université Grenoble Alpes, Grenoble F-38054, France.
authors.forename: Yohann
authors.initials: Y
authors.lastname: Couté
authors.affiliation: INSERM, U1052, CNRS, UMR5286, Centre de Recherche en Cancérologie de Lyon, Equipe «Différenciation Endocrine et Tumorigenèse», Faculté Laënnec, Université Lyon 1, Lyon F-69372, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Massoma
authors.affiliation: INSERM, U1052, CNRS, UMR5286, Centre de Recherche en Cancérologie de Lyon, Equipe «Différenciation Endocrine et Tumorigenèse», Faculté Laënnec, Université Lyon 1, Lyon F-69372, France; Hôpital Edouard Herriot, Service de Chirurgie Digestive, Hospices Civils de Lyon, Lyon F-69437, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Poncet
authors.affiliation: Hôpital Edouard Herriot, Service Central d'Anatomie et Cytologie Pathologiques, Hospices Civils de Lyon, Lyon F-69437, France.
authors.forename: Florian
authors.initials: F
authors.lastname: Lepinasse
authors.affiliation: INSERM, U1052, CNRS, UMR5286, Centre de Recherche en Cancérologie de Lyon, Equipe «Différenciation Endocrine et Tumorigenèse», Faculté Laënnec, Université Lyon 1, Lyon F-69372, France; Hôpital Edouard Herriot, Service Central d'Anatomie et Cytologie Pathologiques, Hospices Civils de Lyon, Lyon F-69437, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Hervieu
authors.affiliation: Fédération de Recherche Santé Lyon-Est, Plateforme Anipath, Faculté Laënnec, Université Lyon 1, Lyon F-69372, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Gadot
authors.affiliation: Département de Biologie Structurale et Bioinformatique, Biomedical Proteomics Research Group, Centre Médical Universitaire, Genève, Switzerland.
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Sanchez
authors.affiliation: INSERM, U1052, CNRS, UMR5286, Centre de Recherche en Cancérologie de Lyon, Equipe «Différenciation Endocrine et Tumorigenèse», Faculté Laënnec, Université Lyon 1, Lyon F-69372, France; Hôpital Edouard Herriot, Service Central d'Anatomie et Cytologie Pathologiques, Hospices Civils de Lyon, Lyon F-69437, France; Fédération de Recherche Santé Lyon-Est, Plateforme Anipath, Faculté Laënnec, Université Lyon 1, Lyon F-69372, France.
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Scoazec
authors.affiliation: INSERM, U1052, CNRS, UMR5286, Centre de Recherche en Cancérologie de Lyon, Equipe «Domaines Nucléaires et Pathologies», Centre Léon Bérard, Université Lyon 1, Lyon F-69373, France.
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Diaz
authors.affiliation: INSERM, U1052, CNRS, UMR5286, Centre de Recherche en Cancérologie de Lyon, Equipe «Différenciation Endocrine et Tumorigenèse», Faculté Laënnec, Université Lyon 1, Lyon F-69372, France. Electronic address: colette.roche@inserm.fr.
authors.forename: Colette
authors.initials: C
authors.lastname: Roche
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003598:Cytoskeletal Proteins / Q000096:biosynthesis*; D019858:Enteroendocrine Cells / Q000378:metabolism* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007414:Intestinal Neoplasms / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D008822:Mice, Transgenic; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D009368:Neoplasm Transplantation; D040901:Proteomics
chemical_list: D003598:Cytoskeletal Proteins; D009363:Neoplasm Proteins
keywords: Cytoskeleton; GEP-NETs; Local invasion; Proteomic; Spectrometry