Identification of cellular targets in human intrahepatic cholangiocarcinoma using laser microdissection and accurate mass and time tag proteomics

Autor: Dos Santos, Alexandre, Court, Magali, Thiers, Valérie, Sar, Sokhavuth, Guettier, Catherine, Samuel, Didier, Bréchot, Christian, Garin, Jérôme, Demaugre, France, Masselon, Christophe
Přispěvatelé: Pathogénèse et traitement de l'hépatite fulminante et du cancer du foie, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'étude de la dynamique des protéomes (LEDyP), Université Joseph Fourier - Grenoble 1 (UJF)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de Virologie - Department of Virology, Institut Pasteur [Paris] (IP), Service d'Anatomie Pathologique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Merieux Alliance, INCA PL027 MIRG-CT-2006-30810, Institut Pasteur [Paris]
Jazyk: angličtina
Rok vydání: 2010
Předmět:
Zdroj: Molecular and Cellular Proteomics
Molecular and Cellular Proteomics, 2010, 9 (9), pp.1991-2004. ⟨10.1074/mcp.M110.000026⟩
Molecular and Cellular Proteomics, American Society for Biochemistry and Molecular Biology, 2010, 9 (9), pp.1991-2004. ⟨10.1074/mcp.M110.000026⟩
ISSN: 1535-9476
1535-9484
Popis: © the American Society for Biochemistry and Molecular Biology"; International audience; Obtaining accurate protein profiles from homogeneous cell populations in heterogeneous tissues can enhance the capability to discover protein biomarkers. In this context, methodologies to access specific cellular populations and analyze their proteome with exquisite sensitivity have to be selected. We report here the results of an investigation using a combination of laser microdissection and accurate mass and time tag proteomics. The study was aimed at the precise determination of proteome alterations in intrahepatic cholangiocarcinoma ICC, a markedly heterogeneous tumor. This cancer, which is difficult to diagnose and carries a very poor prognosis, has shown an unexplained increase in incidence over the last few years. Among a pool of 574 identified proteins, we were able to report on altered abundance patterns affecting 39 proteins conforming to a variety of potential tumorigenic pathways. The reliability of the proteomics results was confirmed by Western blot and immunohistochemistry on matched samples. Most of the proteins displaying perturbed abundances had not yet been described in the setting of ICC. These include proteins involved in cell mobility and actin cytoskeleton remodeling, which may participate in the epithelial to mesenchymal transition, a process invoked in migration and invasion of cancer cells. The biological relevance of these findings was explored using a tissue microarray. An increased abundance of vimentin was thus detected in 70% of ICC and none of the controls. These results suggest that vimentin could play a role in the aggressiveness of ICC and provide a basis for the serious outcome of this cancer.
Databáze: OpenAIRE
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