Waves of cells with an unstable phenotype accelerate the progression of high-grade brain tumors

摘要

In this paper we study a reduced continuous model describing the localevolution of high grade gliomas - a lethal type of primary brain tumor -through the interplay of different cellular phenotypes. We show how hypoxicevents, even sporadic and/or limited in space may have a crucial role on theacceleration of the growth speed of high grade gliomas. Our modeling approachis based on two cellular phenotypes one of them being more migratory and thesecond one more proliferative with transitions between them being driven by thelocal oxygen values, assumed in this simple model to be uniform. Surprisinglyeven acute hypoxia events (i.e. very localized in time) leading to theappearance of migratory populations have the potential of accelerating theinvasion speed of the proliferative phenotype up to speeds close to those ofthe migratory phenotype. The high invasion speed of the tumor persists fortimes much longer than the lifetime of the hypoxic event and the phenomenon isobserved both when the migratory cells form a persistent wave of cells locatedon the invasion front and when they form a evanecent wave dissapearing after ashort time by decay into the more proliferative phenotype. Our findings are obtained through numerical simulations of the modelequations. We also provide a deeper mathematical analysis of some aspects ofthe problem such as the conditions for the existence of persistent waves ofcells with a more migratory phenotype.