Leukemia- Derived Exosomes Induce Migration and Tumor Initiating in Astrocytes from Human Brain Tissue

Background: In children with lymphoblastic leukemia (ALL), cancerous metastasis and involvement of central nervous system (CNS) is common. Despite such commonality, there is insufficient information on the metastasis process, although the role of exosomes as extracellular vesicles on cancer growth and metastasis has been the focus of many studies. Thus, due to the significant presence of astrocytes in the central nervous system, we decided to explore the effect of ALL-derived exosomes on human astrocytes. Methods: In this study, the exosomes, extracted from the surface fluid of Nalm6 cells culture medium after different stages of centrifugation, were identified. Trypan blue staining and scratch methods were used to evaluate the effect of exosomes on the proliferation and invasion of astrocytes. Real-time PCR also analyzed the mRNA expression of cancer-related genes. Results: Astrocytes were treated with concentrations of ALL-derived exosomes (5, 10, 30, and 50 mu g/ml) in the Trypan blue test. According to the results, 50 mu g/ml exosomes led to a significant (P<0.05) differences in the increase of proliferation in the experiment as compared to the control. It was considered as the lowest concentration in other tests. In addition, the results of Scratch test revealed a significant (P<0.01) increase in migration of astrocytes after 24 h. Finally, a significant rise in the expression of MMP9 and Cox2 genes and a considerable decline in P53 in astrocytes exhibited their stimulated and anti-apoptotic phenotype under the impact of ALL-derived exosomes. Conclusion: Exosomes can promote tumor behavior by increasing the expression of tumor-related genes in astrocytes. Therefore, it is necessary to understand the complex factors governing metastasis of leukemia in the CNS for diagnostic and clinical applications.