22 research outputs found
Growth delay of human bladder cancer cells by Prostate Stem Cell Antigen downregulation is associated with activation of immune signaling pathways
<p>Abstract</p> <p>Background</p> <p>Prostate stem cell antigen (PSCA) is a glycosylphosphatidylinositol (GPI) anchored protein expressed not only in prostate but also in pancreas and bladder cancer as shown by immunohistochemistry and mRNA analysis. It has been targeted by monoclonal antibodies in preclinical animal models and more recently in a clinical trial in prostate cancer patients. The biological role played in tumor growth is presently unknown. In this report we have characterized the contribution of PSCA expression to tumor growth.</p> <p>Methods</p> <p>A bladder cell line was engineered to express a doxycycline (dox) regulated shRNA against PSCA. To shed light on the PSCA biological role in tumor growth, microarray analysis was carried out as a function of PSCA expression. Expression of gene set of interest was further analyzed by qPCR</p> <p>Results</p> <p>Down regulation of the PSCA expression was associated with reduced cell proliferation <it>in vitro </it>and <it>in vivo</it>. Mice bearing subcutaneous tumors showed a reduced tumor growth upon treatment with dox, which effectively induced shRNA against PSCA as revealed by GFP expression. Pathway analysis of deregulated genes suggests a statistical significant association between PSCA downregulation and activation of genes downstream of the IFNα/β receptor.</p> <p>Conclusions</p> <p>These experiments established for the first time a correlation between the level of PSCA expression and tumor growth and suggest a role of PSCA in counteracting the natural immune response.</p
Super Resolution Microscopy Reveals that Caveolin-1 Is Required for Spatial Organization of CRFB1 and Subsequent Antiviral Signaling in Zebrafish
10.1371/journal.pone.0068759PLoS ONE87-POLN
Conformation and dynamics of biopharmaceuticals: Transition of mass spectrometry-based tools from academe to industry
Antimicrobials: a global alliance for optimizing their rational use in intra-abdominal infections (AGORA)
Plasma membrane reorganization: A glycolipid gateway for microbes
Ligand-receptor interactions, which represent the core for cell signaling and internalization processes are largely affected by the spatial configuration of host cell receptors. There is a growing piece of evidence that receptors are not homogeneously distributed within the plasma membrane, but are rather pre-clustered in nanodomains, or clusters are formed upon ligand binding. Pathogens have evolved many strategies to evade the host immune system and to ensure their survival by hijacking plasma membrane receptors that are most often associated with lipid rafts. In this review, we discuss the early stage molecular and physiological events that occur following ligand binding to host cell glycolipids. The ability of various biological ligands (e.g. toxins, lectins, viruses or bacteria) that bind to glycolipids to induce their own uptake into mammalian cells by creating negative membrane curvature and membrane invaginations is explored. We highlight recent trends in understanding nanoscale plasma membrane (re-)organization and present the benefits of using synthetic membrane systems. This article is part of a Special Issue entitled: Nanoscale membrane organisation and signalling
Membrane deformation by neolectins with engineered glycolipid binding sites
International audienc
Detachment of Membrane Bound Virions by Competitive Ligand Binding Induced Receptor Depletion
Multivalent
receptor-mediated interactions between virions and
a lipid membrane can be weakened using competitive nonpathogenic ligand
binding. In particular, the subsequent binding of such ligands can
induce detachment of bound virions, a phenomenon of crucial relevance
for the development of new antiviral drugs. Focusing on the simian
virus 40 (SV40) and recombinant cholera toxin B subunit (rCTB), and
using (monosialotetrahexosyl)ganglioside (GM1) as their
common receptor in a supported lipid bilayer (SLB), we present the
first detailed investigation of this phenomenon by employing the quartz
crystal microbalance with dissipation (QCM-D) and total internal reflection
fluorescence (TIRF) microscopy assisted 2D single particle tracking
(SPT) techniques. Analysis of the QCM-D-measured release kinetics
made it possible to determine the binding strength of a single SV40–GM1
pair. The release dynamics of SV40, monitored by SPT, revealed that
a notable fraction of SV40 becomes mobile just before the release,
allowing to estimate the distribution of SV40-bound GM1 receptors
just prior to release
The fucose-binding lectin from opportunistic pathogen <i>Burkholderia ambifaria</i> binds to both plant and human oligosaccharidic epitopes
International audienc