Exosomal lipids impact notch signaling and induce death of human pancreatic tumoral SOJ-6 cells.

Exosomes are of increasing interest as alternative mode of cell-to-cell communication. We previously reported that exosomes secreted by human SOJ-6 pancreatic tumor cells induce (glyco)protein ligand-independent cell death and inhibit Notch-1 pathway, this latter being particularly active during carcinogenesis and in cancer stem cells. Therefore, we asked whether exosomal lipids were key-elements for cell death and hypothesized that cholesterol-rich membrane microdomains were privileged sites of exosome interactions with tumor cells.

A novel tumor-associated pancreatic glycoprotein is internalized by human dendritic cells and induces their maturation.

Aberrant glycosylation or overexpression of cell-surface glycosylated tumor-associated Ags (TAA) distinguish neoplastic from normal cells. Interactions of TAA MUC1 and HER2/neu with dendritic cells (DC) preclude efficient processing, which impairs immune responses. It is thus important to define the mechanisms of interactions between DC and glycosylated TAA and their trafficking and processing for further T cell activation.

Human bile salt-dependent lipase efficiency on medium-chain acyl-containing substrates: control by sodium taurocholate.

Bile salt-dependent lipase was purified to homogeneity from lyophilized human milk and used to screen the influence of the acyl chain length (2-16 carbon atoms) on the kinetic constants k(cat) and K(m) of the hydrolysis of para-nitrophenyl (pnp) ester substrates in the presence or absence of sodium taurocholate (NaTC: 0.02-20 mM). The highest k(cat) value (∼3,500 s(-1)) was obtained with pnpC(8) as substrate, whereas the lowest K(m) (<10 µM) was that recorded with pnpC(10).

Essential role of Notch signaling in apoptosis of human pancreatic tumoral cells mediated by exosomal nanoparticles.

We previously reported that exosomal nanoparticles secreted by human pancreatic tumoral cell lines decrease tumoral cell proliferation through the mitochondria-dependent apoptotic pathway, because of activation of pro-apoptotic phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and of glucose synthase kinase-3beta (GSK-3beta). Interactions between exosomal nanoparticles and cells are thought to involve membrane lipid rafts. However, the underlying mechanism is unknown.

Cyclic AMP signaling as a mediator of vasculogenic mimicry in aggressive human melanoma cells in vitro.

Aggressive melanoma cells can engage in a process termed vasculogenic mimicry (VM) that reflects the ability of tumor cells to express a multipotent, stem cell-like phenotype. Melanoma cell plasticity contributes to the lack of efficient therapeutic strategies targeting metastatic tumors. This study reveals cyclic AMP as a mediator of VM in vitro.

Nuclear localization of a novel human syntaxin 1B isoform.

The syntaxins are proteins associated with various intracellular membrane compartments. They are major participants in a large variety of physiological processes where membrane fusion occurs, including exocytosis. We have identified a novel syntaxin isoform generated by alternative splicing of the human STX1B gene.

Human tumor nanoparticles induce apoptosis of pancreatic cancer cells.

Exosomes are vesicles secreted by most hematopoietic cells on fusion of multivesicular endosomes with the plasma membrane. Many studies have reported that exosomes may also be released by tumor cells. Exosomes are believed to play an antitumor role through immune cells.

In vitro polyphenol effects on activity, expression and secretion of pancreatic bile salt-dependent lipase.

The relationship between cholesterol and atherosclerosis has gained wide credence and red wine polyphenols have been shown to have an anti-atherogenic activity. In the present in vitro studies, we have evaluated and compared the effects of resveratrol, an active compound of red wine, and of a whole red wine polyphenolic extract (RWE) on the pancreatic bile salt-dependent lipase (BSDL). BSDL is involved in the duodenal hydrolysis of lipid esters and in part of cholesteryl esters thus favoring the bioavailability of free cholesterol.

In vitro angiogenic effects of pancreatic bile salt-dependent lipase.

Objective: Bile salt-dependent lipase (BSDL), a lipolytic enzyme secreted in the duodenum by pancreatic acinar cells, has been detected in the serum of all patients and in atheromatous plaque, suggesting its potential implication in vascular pathophysiology.

Methods And Results: In vitro pancreatic BSDL evokes human umbilical vein endothelial cell (HUVEC) proliferation and chemotactic migration. BSDL at mitogen concentration is capable to heal wounded HUVEC monolayer and to promote capillary network formation.

Lectin-like Ox-LDL receptor is expressed in human INT-407 intestinal cells: involvement in the transcytosis of pancreatic bile salt-dependent lipase.

We have recently shown that the pancreatic bile salt-dependent lipase (BSDL) can be taken up by intestinal cells and transported to the blood circulation. This mechanism likely involves (specific) receptor(s) able to bind BSDL and located at the apical intestinal cell membrane. In this study, using Int407 human intestinal cells cultured to form a tight epithelium, we attempted to characterize (the) BSDL receptor(s).

Pancreatic bile salt-dependent lipase induces smooth muscle cells proliferation.

Background: Because bile salt-dependent lipase (BSDL), an enzyme secreted by the pancreatic acinar cells and associated with LDL in circulating blood, also locates with smooth muscle cells (SMCs) in atherosclerotic lesions, we aimed to investigate its effects on SMCs.

Methods And Results: Immunohistochemical experiments allowed us to detect an expression of BSDL in atherosclerotic lesions from hypercholesterolemic monkeys and from human arteries. BSDL was found to be associated with SMCs but not with macrophages.