Extracellular Vesicles Induce Mesenchymal Transition and Therapeutic Resistance in Glioblastomas through NF-κB/STAT3 Signaling

Glioblastoma (GBM) is the most common primary malignant brain tumor and despite optimal treatment, long-term survival remains uncommon. GBM can be roughly divided into three different molecular subtypes, each varying in aggressiveness and treatment resistance. Recent evidence shows plasticity between these subtypes in which the proneural (PN) glioma stem-like cells (GSCs) undergo transition into the more aggressive mesenchymal (MES) subtype, leading to therapeutic resistance. Extracellular vesicles (EVs) are membranous structures secreted by nearly every cell and are shown to play a key role in GBM progression by acting as multifunctional signaling complexes. Here, it is shown that EVs derived from MES cells educate PN cells to increase stemness, invasiveness, cell proliferation, migration potential, aggressiveness, and therapeutic resistance by inducing mesenchymal transition through nuclear factor-κB/signal transducer and activator of transcription 3 signaling. The findings could potentially help explore new treatment strategies for GBM and indicate that EVs may also play a role in mesenchymal transition of different tumor types

Blood platelet RNA enables the detection of multiple sclerosis

Background: In multiple sclerosis (MS), clinical assessment, MRI and cerebrospinal fluid are important in the diagnostic process. However, no blood biomarker has been confirmed as a useful tool in the diagnostic work-up. Objectives: Blood platelets contain a rich spliced mRNA repertoire that can alter during megakaryocyte development but also during platelet formation and platelet circulation. In this proof of concept study, we evaluate the diagnostic potential of spliced blood platelet RNA for the detection of MS. Methods: We isolated and sequenced platelet RNA of blood samples obtained from 57 MS patients and 66 age- and gender-matched healthy controls (HCs). 60% was used to develop a particle swarm-optimized (PSO) support vector machine classification algorithm. The remaining 40% served as an independent validation series. Results: In total, 1249 RNAs with differential spliced junction expression levels were identified between platelets of MS patients as compared to HCs, including EPSTI1, IFI6, and RPS6KA3, in line with reported inflammatory signatures in the blood of MS patients. The RNAs were subsequently used as input for a MS classifier, capable of detecting MS with 80% accuracy in the independent validation series. Conclusions: Spliced platelet RNA may enable the blood-based diagnosis of MS, warranting large-scale validation