THE KYNURENINE PATHWAY AND ITS ROLE IN GLIOBLASTOMA CELL MIGRATION

Abstract AIMS The kynurenine (Kyn) pathway plays an important role in the pathogenesis of many cancers including glioblastomas (GBMs). enzymes, indoleamine-2,3-dioxygenase (IDO1) and tryptophan-2,3-dioxygenase (TDO2), regulate first rate-limiting step resulting formation N-formyl-kynurenine, which is then readily converted into Kyn by formaldehyde. Cancers expressing IDO1 TDO2 enzymes can produce immunosuppressive tryptophan metabolites that compromise host immune system leading to poor patient prognosis. inhibitors TD12, TD18 TD34 were recently developed due lack IDO1/TDO2 inhibitors, block both activity. Here, we investigated ability these novel also target cell migration GBM as part our ongoing research interest this area. METHOD Two established brain tumour lines, U87 U251 one patient-derived line, E55, used determine IC50 values anti-migratory concentrations MTT for application 2D 3D migration/invasion assays. RESULTS Cell all lines was significantly reduced presence inhibitors. E55 appeared be 100-fold more sensitive drug activity; immunofluorescence analysis indicates changes actin cytoskeleton adhesion CONCLUSIONS Initial results suggest play a provide further evidence involvement pathology GBMs. This supports targeting complementary treatment options GBM.