Diffusional instability as a mechanism of tumor invasion

Heterogeneous cell proliferation, migration, and death can be caused by genetic damage and in response to the local microenvironment. Diffusion gradients of oxygen, glucose, metabolites, and drugs, established in the microenvironment during solid tumor growth and response to treatment, can create varying local conditions for subpopulations of tumor cells. Individual cells possess a broad spectrum of survival and migration mechanisms that can be invoked in response to hostile conditions [1], such as hypoxia and hypoglycemia. The consequences of this heterogeneity and variability can be highly multiscalar. Differential cell proliferation, migration, and death along the diffusion gradients affect cell survival and motility properties as a function of these gradients. At the tumor scale, this can lead to invasive fingering and branching and even fragmentation and migration of cell clusters into the surrounding tissue. Thus, these diffusion gradients have an important role in the stability of the tumor morphology.