Project: The role of extracellular vesicles in Glioblastoma Multiforme (GBM) microenvironment modulation
Orlanda Alonso-Martin, Oncología Radioterápica, Hospital Universitario de Salamanca; Adelaida Nieto-Palacios, Oncología Radioterápica, Hospital Universitario de Salamanca; Luis A. Perez-Romasanta, Oncología Radioterápica, Hospital Universitario de Salamanca.
GBM tumor cells produce extracellular vesicles (EVs) containing molecular effectors of several cancer-related processes. There is a growing interest in analyzing EVs from the biofluid of cancer patients as a means of disease diagnosis and therapeutic monitoring. EVs may evolve into a diagnostic platform for the most common form of brain cancer, glioblastoma, with potential clinical translational opportunities.
1. Quantification and characterization of EVs obtained from craniospinal fluid (CSF) and blood, with analysis of proteomic and micro-RNAs profiles
2. Correlation of the quantity and composition of EVs with tumor volume and clinical outcomes: time to progression, survival, and thromboembolic events
Material and Methods
Samples will be obtained immediately before and after surgery, before and after radiotherapy, at the end of Temozolamide treatment and upon tumor progression. EVs will be isolated by ultracentrifugation, scanned by electron microscopy and identified with CD63 western blot. The micro-RNA content will be studied with microarrays. The procoagulant activity will be determined by Zymuphen MP-Activity kit.
The complexity of glioblastoma multiforme (GBM) and its distinct pathophysiology belong to a unique brain microenvironment. Little is known about microRNA-dependent communication between different cellular compartments of the microenvironment that may contribute to the tumor phenotype. EVs emerge as a novel and functionally important vehicle of intercellular communication that can mediate multiple biological effects. In addition, they provide a unique platform to develop molecular biomarkers in brain malignancies.