Anastasia Xagara
Foundation for Research and Technology-Hellas, Greece
Title: Influence of the immunological effector IFNγ in the biology of neuroblastoma cells
Biography
Biography: Anastasia Xagara
Abstract
The immune and nervous systems interact both at the cellular and molecular level, and share significant similarities in essential mechanisms and signaling pathways. IFN-γ, a cytokine that belongs to type II interferons, plays crucial role in innate and adaptive immunity whereas its aberrant expression/activity has been associated with a number of autoimmune diseases. IFNγ can enhance neurogenesis in the hippocampus of adult mice, by unknown mechanisms, possibly involving coordination between brain inflammation and repair, and can also modulate neurotransmitter release at synapses and affect memory, thereby revealing an important role of this immunological effector for the function of the adult nervous system. Using neuroblastoma cells, we are currently analyzing the influence of neuroinflammatory components in the process of aberrant activation of key signaling pathways involved in cellular proliferation and neuronal differentiation as well as in cellular heterogeneity, a hallmark of neuroblastoma which is observed in both tumors and tumor-derived cell lines. We found that IFNγ reduces neuroblastoma cell proliferation by delaying progression through the S phase of the cell cycle. Concomitantly, it promotes molecular and morphological features of early neuronal differentiation as revealed by the extended neurite outgrowth, increased formation of varicosities, and induction of specific neuronal differentiation markers. Our data also showed that chronic treatment with IFNγ alters the program of retinoic acid-induced differentiation, leading to an induction of large, nestin+, Schwann-like (S-type) cells, known to influence the biology of the adjacent neuroblastic (N-type) cells, suggesting that immune components may contribute to the phenotypic heterogeneity and tumorigenicity of neuroblastoma.