Glioblastoma cells extracelular vesicles can reach the bloodstream through an intact bloodbrain barrier
Carrión-Navarro Josefa, Fundación Hospital de Madrid-IMMA, Madrid, Spain; García-Romero Noemí, IMDEA Nanoscience, Madrid, Spain; Esteban-Rubio Susana, Universidad San Pablo CEU, Madrid, Spain; Zafra-Villaverde Antonio, Universidad San Pablo CEU, Madrid, Spain; Prat-Acín Ricardo, Hospital Universitario la Fe, Valencia, Spain; Fernández-Carballal Carlos, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Belda-Iniesta Cristobal, Fundación Hospital de Madrid-IMMA, Madrid, Spain, IMDEA Nanoscience, Madrid, Spain; Ayuso-Sacido Angel, Fundación Hospital de Madrid-IMMA, Madrid, Spain, IMDEA Nanoscience, Madrid, Spain, Universidad San Pablo-CEU, Madrid, Spain.
Glioblastoma multiforme (GBM) is the most common and most malignant brain tumor in adults with an extremely unfavorable prognosis. Recently, it was discovered that cancer initiating cells (CICs) from this type of tumor produce extracellular vesicles (EVs), subdivided in apoptotic bodies (APOs), shedding microvesicles (SMVs) and exosomes (EXOs). These EVs contain proteins, different types of RNA and even genomic DNA, being able to mediate in events such as angiogenesis and intercellular communication. Additionally some authors have reported that EVs are able to cross the leaky blood-brain barrier (BBB) typically found in GBM, and travel through the peripheral blood, where they can be isolated and gDNA sequences might be found. As such, EVs can be used as biomarkers in order to better diagnose and stratify patients and evaluate their response to treatment.
RESULTS AND CONCLUSION
We have found human gDNA from the three types of EVs in the peripheral blood of athymic mice xenografted with CICs isolated from human GBM. Interestingly, when we used CICs characterized by having a diffuse growth pattern within the brain parenchyma, EVs where able to reach the peripheral blood, through an intact BBB. These results suggest that EVs could also cross the BBB to the bloodstream by transcellular migration through endothelial cells.Format: Poster