The activation of Wnt/β-catenin signalling has an important function in gastrointestinal tumorigenesis. It has been suggested that the promotion of Wnt/β-catenin activity beyond the threshold is important for carcinogenesis. We herein investigated the role of macrophages in the promotion of Wnt/β-catenin activity in gastric tumorigenesis. We found β-catenin nuclear accumulation in macrophage-infiltrated dysplastic mucosa of the K19-Wnt1 mouse stomach. Moreover, macrophage depletion in ApcΔ716 mice resulted in the suppression of intestinal tumorigenesis. These results suggested the role of macrophages in the activation of Wnt/β-catenin signalling, which thus leads to tumour development. Importantly, the conditioned medium of activated macrophages promoted Wnt/β-catenin signalling in gastric cancer cells, which was suppressed by the inhibition of tumour necrosis factor (TNF)-α. Furthermore, treatment with TNF-α induced glycogen synthase kinase 3β (GSK3β) phosphorylation, which resulted in the stabilization of β-catenin. We also found that Helicobacter infection in the K19-Wnt1 mouse stomach caused mucosal macrophage infiltration and nuclear β-catenin accumulation. These results suggest that macrophage-derived TNF-α promotes Wnt/β-catenin signalling through inhibition of GSK3β, which may contribute to tumour development in the gastric mucosa.
We used fluorescence flow cytometry to analyze the structural properties of populations of giant liposomes formed by different preparation methods. The inner aqueous volumes and nominal membrane surface areas of a large number of individual liposomes were measured simultaneously by using fluorescent markers. We compared these properties of liposomes prepared by the natural swelling method, the freeze-dried empty liposomes method, and the water-in-oil (W/O) emulsion method. A two-dimensional contour distribution map of the inner volume and the nominal surface area was used to elucidate the structural properties of liposomes over a wide range of liposome sizes. Lamellarity of liposomes was evaluated as the ratio of the nominal surface area to the theoretical surface area calculated from the liposome inner volume. This population analysis revealed the dependency of lamellarity on liposome volume: while the nominal surface areas of populations of liposomes prepared by the natural swelling and the freeze-dried empty liposome methods were widely distributed, those prepared by the W/O emulsion method had a narrower distribution within small values. Furthermore, with the latter method, the nominal surface area varied in proportion to the two-thirds power of the inner volume ranging for several orders of magnitude, indicating the liposomes had a thin membrane, which was constant for the wide volume range. The results as well as the methodology presented here would be useful in designing giant liposomes with desired properties.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.