MET Expressed in Glioma Stem Cells Is a Potent Therapeutic Target for Glioblastoma Multiforme

摘要

Background: Glioblastoma multiforme (GBM) is the most frequent and the most malignant tumor among adult brain tumors. Previous reports led us to hypothesize that the protooncogene mesenchymal-epithelial transition (MET) expressed in glioma stem cell-like cells (GSCs) would be a potent therapeutic target for GBM. Patients and Methods: To address this question, we analyzed 113 original samples of tumors from patients based on immunohistochemistry. During this process, we were able to establish GSC lines from patients with GBM that were MET-positive and MET-negative. Using these cells, we tested the therapeutic impact of a MET inhibitor, crizotinib, both in vitro and in vivo. Results: Patients with MET-positive GBM exhibited poor survival. GSC-based experiments revealed that treatment with crizotinib, both in vitro and in vivo, exhibited therapeutic efficacy particularly against MET-positive GSCs. Conclusion: Based on these findings, we conclude that MET expressed in GSCs might be a potent therapeutic target for GBM.