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Le secretome, un modèle adapté à l'étude des protéines sécrétées par les tumeurs.
Application à l'analyse du rôle joué par p53 sur la sécrétion de protéines par des cellules du cancer du poumon.

Abstract : Cancer is a real public health problem and will represent in 2010 the first cause of mortality. So the knowledge of this disease and its mechanisms remains a great challenge. Malignant processes such as metastasis, invasion, or angiogenesis are tightly dependent on the composition of the extracellular medium, which is itself affected by the release of proteins by the tumor cells. The mutation of pro- and anti-oncogenic factors plays an important role in tumor progression. In this work, we want to ask the following major question: is it interesting to study by proteomics the secreted proteins by tumor to better understand tumorigenesis mechanisms and is it useful for clinical biomarker discovery? We focused on lung cancer which is the cancer with the greater mortality and incidency frequences in the world. This cancer has the greater p53 mutation rates. This protein is a major tumor suppressor known to modulate the release of proteins by the tumor cells; however, while p53-modulated intracellular proteins have been extensively studied, little is known concerning their extracellular counterparts. Here, we developed a proteomics process using iTRAQ labeling, OFFGEL isoelectric focusing and LC-MALDI-MS/MS analysis efficient to the study of this class of proteins. We used it to characterize the p53-dependent secretome of a lung tumor model in vitro. We identified 909 proteins released by these cells, among which 91 are p53-modulated. This differential secretome analysis promises more detailed of how the loss of wt-p53 contributes to tumorigenic processes through the modulation of secreted proteins. We also demonstrated that the modulation of exported proteins can be detected in vivo in total protein extracts and plasma of tumor-bearing mice. This is the first report establishing that the in vitro cell line secretome is reliable and reflects the extracellular release of proteins from tumor cells in vivo and could be used to identify putative tumor markers.
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https://tel.archives-ouvertes.fr/tel-00402098
Contributor : Jérôme Chenau <>
Submitted on : Monday, July 6, 2009 - 4:28:35 PM
Last modification on : Friday, November 6, 2020 - 4:02:25 AM
Long-term archiving on: : Saturday, November 26, 2016 - 10:26:45 AM

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  • HAL Id : tel-00402098, version 1

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U823 | UJF | UGA

Citation

Jérôme Chenau. Le secretome, un modèle adapté à l'étude des protéines sécrétées par les tumeurs.
Application à l'analyse du rôle joué par p53 sur la sécrétion de protéines par des cellules du cancer du poumon.. Sciences du Vivant [q-bio]. Université Joseph-Fourier - Grenoble I, 2009. Français. ⟨tel-00402098⟩

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