Phosphatidylcholine-Specific Phospholipase C Activation in Epithelial Ovarian Cancer Cells

Spadaro, Francesca; Ramoni, Carlo; Mezzanzanica, Delia; Miotti, Silvia; Alberti, Paola; Cecchetti, Serena; Iorio, Egidio; Dolo, Vincenza; Canevari, Silvana; Podo, Franca

doi:10.1158/0008-5472.can-07-6763

Cited by 87 publications

(102 citation statements)

References 47 publications

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“…Those studies reported that AGTR2 could block AGTR1-mediated signal transduction by negative cross-talk via the phosphorylation of PLC β 3 in the cytoplasm, rather than by the direct interaction on the cell surface. Activation of PLC β 3 mediates signal transduction for tumor progression in various cancer cell types including epithelial ovarian carcinoma [29,30]. Consistent with those findings, we observed that Ang II increased the expression of phosphorylated PLC β 3 and either losartan or CGP42112A blocked those increases.…”

Section: Discussionsupporting

confidence: 90%

Dual targeting of angiotensin receptors (AGTR1 and AGTR2) in epithelial ovarian carcinoma

Park

Choi

et al. 2014

Gynecologic Oncology

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Section: Discussionsupporting

confidence: 90%

Dual targeting of angiotensin receptors (AGTR1 and AGTR2) in epithelial ovarian carcinoma

Park

Choi

et al. 2014

Gynecologic Oncology

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“…20 Blots were incubated with rabbit anti-OVA and anti-NOX-2 Abs (Abcam). Actin was used as quantitative loading control (mouse anti-actin was from Sigma-Aldrich).…”

Section: Western Blot Analysismentioning

confidence: 99%

IFN-α enhances cross-presentation in human dendritic cells by modulating antigen survival, endocytic routing, and processing

Spadaro

Lapenta

Donati

et al. 2012

Blood

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125

112

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IntroductionOver the past years, it has become apparent that type-I interferons (IFNs) affect adaptive immunity through their effects on monocytes. In particular, IFN-␣ has been shown to act as a potent inducer of the rapid differentiation of human monocytes into highly activated and partially mature dendritic cells (DCs), known as IFN-DCs. 1 We demonstrated previously that human monocytes exposed to granulocyte macrophage colony-stimulating factor (GM-CSF) and IFN-␣ are rapidly induced to express a set of membrane molecules involved in antigen (Ag) presentation and T-cell costimulation, as well as to strongly promote T helper (Th)-1 response and CD8 ϩ T cell cross-priming. 2 Moreover, IFN-DCs were shown to cross-present very efficiently low amounts of nonstructural-3 protein (NS3) of hepatitis C virus (HCV) to a specific CD8 ϩ T cell clone, even in the absence of CD4 ϩ T-cell help. 2 The cross-presentation efficiency of DCs is not dictated solely by their Ag capture capability 3 ; it also is affected by critical factors such as (1) the route of Ag uptake, (2) acidification-sensitive Ag degradation in endosomal-lysosomal compartments, and (3) Ag entry into the major histocompatibility complex class-I (MHC-I) pathway. [4][5][6][7][8] At present, 4 nonmutually exclusive models have been proposed to explain cross-presentation. [8][9][10] In the canonical cytosolic pathway, endocytosed Ags are translocated into the cytosol, where they are degraded by the proteasome, and then the antigenic peptides are transported into the lumen of the endoplasmic reticulum (ER) by the transporters associated with Ag processing (TAPs), 9,10 or alternatively, reimported from the cytoplasm into the early endosomes and loaded onto endosomal 12 According to a less well-defined TAP-and proteasomeindependent endosomal pathway, Ags can be processed by endosomal proteases and loaded onto MHC-I molecules directly within early and late endosomes and lysosomes. [13][14][15] An additional model involves the delivery of components of the ER to endocytic organelles or the transport of incoming Ags to the ER. [16][17][18] Here, we have investigated the mechanisms underlying the superior efficiency of IFN-DCs in the cross-presentation of soluble proteins, by studying (1) the Ag uptake and trafficking to the class-I processing pathway, (2) the maturation kinetic of the organelles containing the internalized proteins, (3) the Ag stability within endosomes, and (4) the Ag processing and cross-presentation to specific CD8 ϩ T cells. The results reveal that IFN-DCs exhibit a delayed endosomal acidification associated with a prolonged Ag survival and retention in the early endosomal compartment, as well as with Ag trafficking to recycling pathways. In IFN-DCs, both early and recycling endosomal compartments serve as important stores of MHC-I molecules, allowing rapid presentation of exogenous Ags. These findings provide novel mechanistic insight into the cross-presentation efficiency of IFN-DCs and underscore the potential advantage of using these cellula...

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“…Enzymes such as sphingosine kinases, sphingomyelinases, ceramidases, lipid kinases and phosphatases, and phospholipases are altered in cancer tissues [12,16,19,34,36,37,75,76]. These proteins by themselves might not represent ideal biomarkers, unless they are liberated into the blood stream or urine.…”

Section: Functional Validation Of Surrogate Biomarkersmentioning

confidence: 99%

Lipid-based biomarkers for cancer

Fernandis

Wenk

2009

Journal of Chromatography B

101

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Phosphatidylcholine-Specific Phospholipase C Activation in Epithelial Ovarian Cancer Cells

Cited by 87 publications

References 47 publications

Dual targeting of angiotensin receptors (AGTR1 and AGTR2) in epithelial ovarian carcinoma

Dual targeting of angiotensin receptors (AGTR1 and AGTR2) in epithelial ovarian carcinoma

IFN-α enhances cross-presentation in human dendritic cells by modulating antigen survival, endocytic routing, and processing

Lipid-based biomarkers for cancer

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