Institute for Experimental Cancer Research, University of Kiel and University Hospital Schleswig-Holstein, Campus Kiel, Arnold-Heller-Str. 3, 24105, Kiel, Germany.
Pharmaceutical Institute, Department of Pharmaceutical Biology, University of Kiel, Gutenbergstraße 76, 24118, Kiel, Germany.
Carbohydr Res. 2020 Apr;490:107903. doi: 10.1016/j.carres.2019.107903. Epub 2019 Dec 23.
This study intends to investigate the inhibitory potential of different plant derived saccharides on cell migration and adhesion of pancreatic ductal adenocarcinoma (PDAC) cells to microvascular liver endothelium, particularly considering the role of transmembranous galectin-3. PDAC cell lines PancTu1 and Panc1 were characterized by considerable (transmembranous) galectin-3 (Gal3) expression. SiRNA mediated Gal3 knockdown as well as treatment with differentially processed pectins and arabinogalactan-proteins (AGPs) did not impact on cell migration of either PDAC cell line. In contrast, Gal3 knockdown reduced adhesion of PDAC cells to the liver endothelial cell line TMNK-1 being more pronounced in Panc1 cells. Similarly, plant derived substances did not impact cell adhesion of PancTu1 cells while partially hydrolyzed citrus pectin (MCP), pectinase-treated MCP (MCP) and partially hydrolized AGP (AGP) clearly diminished adhesive properties of Panc1 cells. MCP or AGP could not further intensify the adhesion reducing effect of galectin-3 knockdown, indicating that these plant derived polysaccharides are able to inhibit PDAC cell adhesion to liver endothelial cells in a galectin-3 dependent manner. Overall, these data suggest an inhibitory potential of plant derived processed saccharides which have undergone chemical modification in impairing PDAC cell adhesion to liver endothelium.
本研究旨在探讨不同植物来源的糖对胰腺导管腺癌(PDAC)细胞迁移和黏附至微血管肝内皮细胞的抑制潜力,特别考虑跨膜半乳糖凝集素-3(Galectin-3)的作用。PDAC 细胞系 PancTu1 和 Panc1 表现出相当程度的(跨膜)Galectin-3(Gal3)表达。通过 siRNA 介导的 Gal3 敲低以及用不同处理的果胶和阿拉伯半乳聚糖蛋白(AGP)进行处理,均未影响两种 PDAC 细胞系的迁移。相反,Gal3 敲低减少了 PDAC 细胞与肝内皮细胞系 TMNK-1 的黏附,在 Panc1 细胞中更为明显。同样,植物来源的物质对 PancTu1 细胞的黏附没有影响,而部分水解的柑橘果胶(MCP)、果胶酶处理的 MCP(MCP)和部分水解的 AGP(AGP)则明显降低了 Panc1 细胞的黏附特性。MCP 或 AGP 不能进一步增强 Galectin-3 敲低的黏附减少作用,表明这些植物来源的多糖能够以 Galectin-3 依赖的方式抑制 PDAC 细胞黏附至肝内皮细胞。总的来说,这些数据表明,经过化学修饰的植物来源的加工糖具有抑制 PDAC 细胞黏附至肝内皮的潜力。