Naoki Ohtsu
Hokkaido University, Japan
Title: Inhibition of Eva1 degrade the formation and development of glioblastomas
Biography
Biography: Naoki Ohtsu
Abstract
Research focused on the property and targets of cancer stem cells, which have tumorigenicity and treatment-resistant, may contribute to the discovery of new therapeutic and diagnostic strategies. We have previously established mouse glioma-initiating cell (mGIC) lines from normal neural lineage cells, analyzed their gene expression profile, and reported functions of GIC-specific genes. We further focused on GIC-specific membrane proteins and found uncharacterized cell-membrane protein Eva1. Here we show the characterization of Eva1 in GIC: Eva1 is highly expressed in mouse GIC line, NSCL61, and human glioblastoma (GBM, WHO grade IV)-derived floating spheres, whereas it is not expressed in normal adult mouse and human brain. Eva1 expression is correlated with the malignancy of glioma. Indeed, we found that Eva1+ cells disseminate in human GBM tissue. Moreover, knockdown of Eva1 inhibited cell proliferation and tumorigenicity in mGIC and hGIC. Forced-expression of Eva1 enhanced malignancy of Low-grade human glioma (Diffuse Astrocytoma: DA, WHO grade II). The combination of polyclonal anti-Eva1 antibody and cytotoxic factor Saporin kills GIC, therefore it promised as a new target of antibody preparation. Using gene expression profiles between mGIC and Eva1-knockdown mGIC, we further found Eva1 signal pathway. Eva1 induced GIC proliferation through the activation of the RelB-dependent noncanonical NF-kB pathway by recruiting TRAF2 to the cytoplasmic tail. This signal pathway is important for human GBM formation. Taken together, these findings suggest that Eva1 is a potential target for immunotherapy.