Collective invasion of glioma cells through OCT1 signalling and interaction with reactive astrocytes after surgery.

摘要: Glioblastoma multiforme (GBM) is the most aggressive form of brain cancer with a short median survival time. GBM characterized by hallmarks proliferation and cellular infiltration normal tissue. miR-451 its downstream molecules are known to play pivotal role in regulation balance invasion response metabolic stress tumour microenvironment (TME). Surgery-induced transition reactive astrocyte populations can significant dynamics. In this work, we develop multi-scale mathematical model miR-451-LKB1-AMPK-OCT1-mTOR pathway signalling individual cell dynamics astrocytes after surgery. We show how effects fluctuating glucose on cells need be reprogrammed taking into account recent history variations an AMPK/miR-451 reciprocal feedback loop. The shows availability significantly affect activity and, turn, lead critical migration. also predicts that microsurgery primary induces phenotypical changes stem cell-like promoting migration Cxcl5. Finally, investigated new anti-tumour strategy Cxcl5-targeting drugs. This article part theme issue 'Multi-scale analysis modelling collective biological systems'.