A phenotype-structured model to reproduce the avascular growth of a tumor and its interaction with the surrounding environment.

ABSTRACT

We here propose a one-dimensional spatially explicit phenotype-structured model to analyze selected aspects of avascular tumor progression. In particular, our approach distinguishes viable and necrotic cell fractions. The metabolically active part of the disease is, in turn, differentiated according to a continuous trait, that identifies cell variants with different degrees of motility and proliferation potential. A parabolic partial differential equation (PDE) then governs the spatio-temporal evolution of the phenotypic distribution of active cells within the host tissue. In this respect, active tumor agents are allowed to duplicate, move upon haptotactic and pressure stimuli, and eventually undergo necrosis. The mutual influence between the emerging malignancy and its environment (in terms of molecular landscape) is implemented by coupling the evolution law of the viable tumor mass with a parabolic PDE for oxygen kinetics and a differential equation that accounts for local consumption of extracellular matrix (ECM) elements. The resulting numerical realizations reproduce tumor growth and invasion in a number scenarios that differ for cell properties (i.e., individual migratory behavior, duplication, and mutation potential) and environmental conditions (i.e., level of tissue oxygenation and homogeneity in the initial matrix profile). In particular, our simulations show that, in all cases, more mobile cell variants occupy the front edge of the tumor, whereas more proliferative clones are selected at more internal regions. A necrotic core constantly occupies the bulk of the mass due to nutrient deprivation. This work may eventually suggest some biomedical strategies to partially reduce tumor aggressiveness, i.e., to enhance necrosis of malignant tissue and to promote the presence of more proliferative cell phenotypes over more invasive ones.