Role of exosomes in malignant transformation of astrocytes

Glioblastoma multiforme (GBM) is the mainly common type of primary brain tumors with dismal prognosis. Every year, nearly 3 people out of 100.000 become affected by the disease. Glioblastomas belong to the group of astrocytomas which originate purely from astrocytic cells in the brain parenchyma and usually do not affect neurons. The World Health Organization (WHO) classifies the gliomas into four grades according to their morphologies and the severity of their malignant behavior. Exosomes are the small nanovesicles which are known to be released by all cell types and are present in all biological fluids. Proteins, lipids, mRNA and miRNA molecules can be transported with exosomes. They thereby have specialized functions in a variety of key biological processes like intercellular genetic and metabolic communication as well as modulation of immune responses. Recently, their role in cancer and other pathological conditions has gained more attention. Their content has been studied in GBM as well as other cancer cells and they are considered as potential diagnostic biomarkers. However, their role in diffuse glioblastoma invasion has been overlooked. In this study human astrocyte cells (NHA) cells were treated with exosomes harvested from commercially available cell lines of GBM which are U87-MG and A172. Phenotypic and behavioral changes of NHAs were observed and analyzed. These changes were determined by cell proliferation assays (like MTS and EDU), cell cycle analysis, real-time PCR, TG2 Elisa, Western Blotting and as well as direct monitoring via live cell imaging. The obtained results were shown that GBM-derived exosomes play important role in invasion and metastasis. Only a few studies have been published about the possible mechanism of exosomes in diffuse glioblastoma invasion. We think that understanding the intercellular communication of exosomes will open a new approach in the desperate search of therapeutic options for glioblastomas. The next step should include in vivo studies to shed light on the role of exosomes in GBM invasion in CNS.