Exosome‐mediated extracellular release of polyadenylate‐binding protein 1 in human metastatic duodenal cancer cells

Abstract

Exosomes are small vesicles secreted from cells that transport their embedded molecules through bidirectional exocytosis- and endocytosis-like pathways. Expression patterns of exosomal molecules such as proteins and RNAs can be indicative of cell type since their signature is thought to be unique among cells. Using human primary (AZ-521) and metastatic (AZ-P7a) duodenal cancer cell lines, we conducted a comparative exosomal proteome analysis to identify proteins with metastatic marker potential. As determined by LC-MS/MS and Western blot analyses, polyadenylate-binding protein 1 (PABP1) was found to be predominantly abundant in AZ-P7a exosomes. The amount of exosomal PABP1 in AZ-P7a cells increased by treating the cells with inhibitors for the classical ER/Golgi secretory pathway (brefeldin A and monensin) and the ubiquitin-proteasome pathway (MG-132 and PYR-41). Treatment of AZ-P7a cells with the neutral sphingomyelinase inhibitor GW4869, which suppresses exosome release, not only reduced the amount of exosomal PABP1 but also produced PABP1-immunoreactive products cleaved via a proteolysis-like process. Taken together, these results suggest that AZ-P7a cells do not tolerate intracellular PABP1 accumulation and are thus exported into the extracellular milieu by the exosome-mediated pathway. In addition, PABP1 has a potential use as a biomarker for metastatic duodenal cancer.

Exosomes miR-126a released from MDSC induced by DOX treatment promotes lung metastasis

“…5C ). The treatment of MDSCs with GW4869 that was reported to inhibit the secretion of exosome from cells 8, 31 resulted in reduction of miR-126a secreted in the exosomes of the DOX-treated MDSC (Supplementary Fig. 5D ).…”

Selective release of miRNAs via extracellular vesicles is associated with house‐dust mite allergen‐induced airway inflammation

“…We hypothesized that the reduction in exosome secretion in the airways may suppress allergic airway inflammation. GW4869, an inhibitor of neutral sphingomyelinase (nSMase), has been reported to significantly decrease the release of exosomes from cells . To test our hypothesis, we used GW4869 in the murine asthma model.…”

Supplementation with small-extracellular vesicles from ovarian follicular fluid during in vitro production modulates bovine embryo development

“…Additionally, we determined the presence of PABP a mRNA stabilizing protein. The presence of PABP protein in extracellular vesicles was identified in human duodenal cancer cells, although the function is not clear [36]. The presence of PABP in EVs present in follicular cells may indicate that mRNAs present within EVs are stabilized and could possibly be translated, suggesting an important role for these molecules within these vesicles.…”