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Mol Cell Endocrinol. 2015 Jan 5;399:154-63. doi: 10.1016/j.mce.2014.09.006. Epub 2014 Sep 16.

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.

Author information

1
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.
2
INSERM, U1038, CEA iRTSV, Biologie à Grande Echelle, Université Grenoble Alpes, Grenoble F-38054, France.
3
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.
4
Hôpital Edouard Herriot, Service Central d'Anatomie et Cytologie Pathologiques, Hospices Civils de Lyon, Lyon F-69437, France.
5
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.
6
Fédération de Recherche Santé Lyon-Est, Plateforme Anipath, Faculté Laënnec, Université Lyon 1, Lyon F-69372, France.
7
Département de Biologie Structurale et Bioinformatique, Biomedical Proteomics Research Group, Centre Médical Universitaire, Genève, Switzerland.
8
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.
9
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.
10
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.

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.

KEYWORDS:

Cytoskeleton; GEP-NETs; Local invasion; Proteomic; Spectrometry

PMID:
25224486
DOI:
10.1016/j.mce.2014.09.006
[Indexed for MEDLINE]

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