Abstract 274: Deciphering the role of tumor-released microvesicles in glioblastoma mobility and invasion

Abstract

Abstract To promote cell growth, invasion and therapy resistance, glioblastoma (GBM) makes use of different communication routes with the neighbor environment which include Extracellular Vesicles (EVs). EVs are a heterogeneous group of cell-released membranous structures, which contain a wide mixture of active molecules. Each cell type secretes a unique combination of different EV subpopulations that vary in size, content and function. In GBM, the subfraction of small-EVs derived from multivesicular bodies, also referred as exosomes (EXOs), have received considerable attention for their capacity to create a tumor-supportive microenvironment through their actions on immune cells, vasculature and glial cells. Only recently it has been observed that large-EVs formed by the budding of the cell membrane, classically called microvesicles (MVs), are more abundant than EXOs in the plasma of GBM patients. Large-MVs have been associated with disease progression in the context of prostate cancer, but their functional significance remain largely uncharacterized in GBM. To explore EV migratory potential in the GBM context, an in vitro migration test performed on spheroids of patient-derived Glioma Stem-like Cells (GSC) has been set up. EXOs from GSC culture supernatants exert no migratory effects, whereas MVs triggered remarkable cell migration. Differently from GSC culture supernatants, both EXOs and MVs isolated from surgical washing exerted a remarkable migratory effect suggesting that not only EVs from tumoral cells are actively implicated in GSC mobility but also EVs from the non-tumoral microenvironment act synergistically to sustain GBM invasion. To better understand the contribution of the cell sub-population of the tumor environment, an EV separation based on CD45(leukocyte common antigen) expression was performed. CD45-positive EVs (released by immune cells) and CD45-negative EVs (released by tumor and stroma cells) were employed in the spheroid migration assay. Results showed the absence of any migratory effect of CD45-positive subsets, both EXOs and MVs, indicating that EVs selectively generated by tumor and stroma cells play a key role in tumoral invasion. Furthermore, a multiplex bead-based flow-cytometry analysis performed on EVs from six GBM patients revealed the presence of specific antigen clusters related to migration and could also be investigated as tumoral biomarkers in a liquid biopsy context. Citation Format: Valentino Ribecco, Matteo Tamborini, Elisabetta Stanzani, Marco Pizzocri, Milena Mattioli, Simone Olei, Maria Pia Tropeano, Federico Pessina, Michela Matteoli, Lorena Passoni. Deciphering the role of tumor-released microvesicles in glioblastoma mobility and invasion [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 274.