Insight into the Exosomal Membrane: From Viewpoints of Membrane Fluidity and Polarity.

Numerous research studies have been done for exosomes, particularly focusing on membrane proteins and included nucleic acids, and the volume of the knowledge about the lipids in the exosomal membrane has been increasing. However, the dynamic property of the exosomal membrane is hardly studied. By employing milk exosome as an example, herein the exosomal membrane was characterized focusing on the membrane fluidity and polarity. The lipid composition and phase state of milk exosome (exosome from bovine milk) were estimated. The milk exosome contained enriched Chol (43.6 mol % in total lipid extracts), which made the membrane in the liquid-ordered (lo) phase by interacting with phospholipids. To suggest a model of exosomal vesicle cargo, the liposome compositions that mimic milk exosome were studied: liposomes were made of cholesterol (Chol), milk sphingomyelin (milk SM), and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC). By using fluorescent probes 1,6-diphenyl-1,3,5-hexatriene and 6-dodecanoyl-2-dimethylaminonaphthalene, the microenvironments of submicron-sized membranes of exosome and model liposomes were investigated. The membrane fluidity of milk exosome was slightly higher than those of Chol/milk SM/POPC liposomes with a similar content of Chol, suggesting the presence of enriched unsaturated lipids. The most purposeful membrane property was obtained by the liposome composition of Chol/milk SM/POPC = 40/15/45. From the above, it is concluded that Chol is a fundamental component of the milk exosomal membrane to construct the enriched lo phase, which could increase the membrane rigidity and contribute to the function of exosome.

Expression of liver X receptors in normal and refractory carcinoma tissues of the human lung and pancreas.

Liver X receptors (LXRs) participate not only in maintaining cholesterol homeostasis but also in controlling cellular growth in many types of normal and tumor cells. We previously reported that LXRα was aberrantly expressed in human oral squamous cell carcinoma (HOSCC) tissues and cell lines, and that LXR stimulation led to significant reduction of proliferation of HOSCC cells via accelerating cholesterol efflux. Since LXRs and downstream proteins involved in cholesterol metabolism could be also applied as therapeutic targets in small cell lung carcinoma (SCLC) and pancreatic ductal adenocarcinoma (PDAC), we herein analyzed the distribution of LXR proteins in these refractory cancers as well as in normal human lung and pancreatic tissues. LXRß was observed in ciliated epithelial cells, bronchial gland epithelia, type II alveolar epithelia and alveolar macrophages of the lung, and was less expressed in bronchial basal cells and type I alveolar epithelia. In addition, LXRß was detected in epithelium of the pancreatic duct and acinar cells of the pancreas, and was weakly expressed in pancreatic islet cells. By contrast, LXRα expression was restricted to alveolar macrophages, and was not evident in any types of epithelial cells in the lung and pancreas. We also demonstrated that LXRß but not LXRα was abundantly expressed in nine cases of SCLC and twenty cases of PDAC tissues. These findings provide basic information for evaluating the efficacy of LXR-targeted treatment in SCLC and PDAC.