Cell surface metalloproteases as targets in glioblastoma: implications for tumor growth and therapy resistance

Background: Despite multimodal therapy, Glioblastoma (GBM) chemotherapy with Temozolomide (TMZ) remains inefficient due to chemoresistance. MMP and ADAM metalloproteases (MPs) are increased in GBM and could contribute to chemoresistance and TMZ induced recurrence of glioblastoma. Methods: TMZ sensitivity of GBM cells was assessed with MP inhibitors batimastat (BB-94) and marimastat (BB-2516). Induction of MPs by TMZ was determined by qPCR and activity assays. MP-dependent effects of TMZ on mitochondria and intracellular kinase (Akt/PI3K, ERK1/2) pathway were investigated by FACS, morphological analysis and Weste…