Dataset Information

Proteomics of Primary cells derived from Ovarian Cancer

ABSTRACT: We analyzed primary cells derived from patients with ovarian cancer. We compared OSE, FTE and EOC and we use quantitative propeomics followed by WB, IHC, TMA for validation of our findings. We also analyzed the phosphoproteome of OVCAR3.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Primary Cell

DISEASE(S): Malignant Neoplasm Of Ovary

SUBMITTER: Chiara Francavilla

LAB HEAD: Jesper V. Olsen

PROVIDER: PXD003531 | Pride | 2017-04-03

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	20130603_QE3_UPLC9_CFR_SA_OC_P_AS_01_02.raw	Raw
	20130603_QE3_UPLC9_CFR_SA_OC_P_AS_01_03.raw	Raw
	20130603_QE3_UPLC9_CFR_SA_OC_P_AS_03_02.raw	Raw
	20130603_QE3_UPLC9_CFR_SA_OC_P_AS_03_03.raw	Raw
	20130603_QE3_UPLC9_CFR_SA_OC_P_AS_04.raw	Raw

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Publications

Phosphoproteomics of Primary Cells Reveals Druggable Kinase Signatures in Ovarian Cancer.

Francavilla Chiara C Lupia Michela M Tsafou Kalliopi K Villa Alessandra A Kowalczyk Katarzyna K Rakownikow Jersie-Christensen Rosa R Bertalot Giovanni G Confalonieri Stefano S Brunak Søren S Jensen Lars J LJ Cavallaro Ugo U Olsen Jesper V JV

Cell reports 20170301 13

Our understanding of the molecular determinants of cancer is still inadequate because of cancer heterogeneity. Here, using epithelial ovarian cancer (EOC) as a model system, we analyzed a minute amount of patient-derived epithelial cells from either healthy or cancerous tissues by single-shot mass-spectrometry-based phosphoproteomics. Using a multi-disciplinary approach, we demonstrated that primary cells recapitulate tissue complexity and represent a valuable source of differentially expressed ...[more]

PMID: 28355574

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Project description:Epithelial ovarian carcinoma (EOC) is an aggressive tumor often diagnosed at an advanced stage, when there is little prospect for cure. Despite some advances in surgical and chemotherapeutic strategies, only marginal improvements in patient outcome have been obtained. Hence, understanding the biological mechanisms underpinning EOC progression is critical for its treatment and to ameliorate patients survival. Recently, we reported that CD157 is expressed in EOC and controls tumor cell migration and invasion. Using stable overexpression and knockdown in OVCAR-3 and OV-90 ovarian cancer cell lines, we demonstrated that CD157 overexpression promotes morphological and functional changes, characterized by downregulation of epithelial marker and upregulation of mesenchymal ones. These are mediated at the transcriptional level by altering the expression of Snail and Zeb1 transcriptional repressors. The effects of CD157 overexpression on ovarian cancer phenotype translate into increased tumor cell motility and mesotelial invasion, while its knockdown significantly reduces the migratory potential, implying a direct correlation between CD157 expression levels and EOC aggressiveness. The analysis of the transcriptomic profiling highlighted 378 significantly differentially expressed genes, representing the signature of CD157-overexpressing EOC cells. The overall picture deduced from the analysis of these modulated transcripts indicated that high CD157 expression results in strengthening of a number of biological functions that favour tumor progression (including cell differentiation, cell motility and migration), and weakening of selected biological processes that hinder the tumor progression (such as apoptosis, cell death and response to stress). Collectively, these data support a causal role of CD157 in the control of ovarian cancer progression motivating the existence of a direct correlation between the expression levels of CD157 and the adverse clinical outcome in EOC patients, and suggest that CD157 may represent a valuable therapeutic target. Gene expression analysisi of control cell lines (OVCAR-3/mock and OV-90/mock) and testing cell lines (OVCAR-3/CD157 and OV-90/CD157), with two replicates, with dye swap, performed for each sample.